Yoshiya Toyoda

Initial Experience With Single Cannulation for Venovenous Extracorporeal Oxygenation in Adults

PURPOSEnHistorically, venovenous extracorporeal membrane oxygenation has required dual cannulation. A single-venous cannulation strategy may facilitate implantation and patient mobilization. Here we present our early experience with a single cannulation technique.nnnDESCRIPTIONnReview of venovenous extracorporeal membrane oxygenation support using internal jugular vein insertion of the Avalon elite bicaval dual lumen catheter (Avalon Laboratories, Rancho Dominguez, CA) in 11 consecutive patients with severe respiratory failure.nnnEVALUATIONnAdequate oxygenation was obtained in all patients: 115 mm Hg PaO(2) (median), 53 to 401 mm Hg (range). Median time of support was 78 hours (range, 3 to 267 hours). No mortality was directly related to the cannulation strategy. There were three nonfatal cannulation-related events. Two patients had proximal cannula displacement requiring repositioning. One patient suffered an acute thrombosis of the cannula.nnnCONCLUSIONSnOur series supports single-venous cannulation in venovenous extracorporeal membrane oxygenation as a promising technique. It may be an excellent alternative to current cannulation strategies in patients requiring prolonged support and specifically for those considered for a bridge-to-lung transplantation.

Myocardial protection by PJ34, a novel potent poly (ADP-ribose) synthetase inhibitor.

BACKGROUNDnThe activation of poly (ADP-ribose) synthetase plays an important role in the pathogenesis leading to myocardial ischemia-reperfusion injury. The aim of this study was to determine if a novel potent inhibitor of poly (ADP-ribose) synthetase, PJ34, provides myocardial protection.nnnMETHODSnPigs were subjected to 60 minutes of regional ischemia followed by 180 minutes of reperfusion. Ten mg/kg of PJ34 (PJ34; n = 6) was administrated intravenously (treated group) from 15 to 5 minutes before reperfusion followed by 3 mg/kg/hour of PJ34 from 5 minutes before reperfusion to the end of 180 minutes reperfusion. Control pigs (n = 7) received vehicle only. Arterial and left ventricular pressure and coronary flow were monitored.nnnRESULTSnThe PJ34 showed significant reduction on infarct size (37.5%+/-4.5% and 50.5%+/-4.8% of the area at risk) for PJ34 and control pigs groups, respectively, (p < 0.05). Significant reduction in postsystolic shortening, as well as improvement on segment shortening, and positive first derivative of pressure over time (+dP/dt) maximum were also observed in PJ34 versus control pigs (p < 0.05).nnnCONCLUSIONSnOur results suggest that PJ34 provides cardioprotection by decreasing myocardial infarct size and enhancing postischemic regional and global functional recovery.

Selective opening of mitochondrial ATP-sensitive potassium channels during surgically induced myocardial ischemia decreases necrosis and apoptosis

OBJECTIVEnMitochondrial ATP-sensitive potassium channels have been proposed to be myoprotective. The relevance and specificity of this mechanism in cardiac surgery was unknown. The purpose of this study was to examine the effects of the mitochondrial potassium ATP-sensitive channel opener diazoxide on regional and global myocardial protection using a model of acute myocardial infarction.nnnMETHODSnPigs (n=19) were placed on total cardiopulmonary bypass and then subjected to 30 min normothermic regional ischemia by snaring the left anterior descending coronary artery (LAD). The aorta was then crossclamped and cold blood Deaconess Surgical Associates cardioplegia (DSA; n=6) or DSA containing 50 microM diazoxide (DZX; n=6) was delivered via the aortic root and the hearts subjected to 30 min hypothermic global ischemia. The crossclamp and snare were removed and the hearts reperfused for 120 min.nnnRESULTSnNo significant differences in preload recruitable stroke work relationship, Tau, proximal, distal or proximal/distal coronary flow, regional or global segmental shortening, systolic bulging or post-systolic shortening were observed within or between DSA and DZX hearts during reperfusion. Infarct was present only in the region of LAD occlusion in both DSA and DZX hearts. Infarct size (% of area at risk) was 33.6+/-2.9% in DSA and was 16.8+/-2.4% in DZX hearts (P<0.01 versus DSA). Apoptosis as estimated by TUNEL positive nuclei was 120.3+/-48.8 in DSA and was significantly decreased to 21.4+/-5.3 in DZX hearts. Myocardial infarct was located centrally within the area at risk in both DSA and DZX hearts but was significantly increased at borderline zones within the area at risk in DSA hearts.nnnCONCLUSIONSnThe addition of diazoxide to cardioplegia significantly decreases regional myocardial cell necrosis and apoptosis in a model of acute myocardial infarction and represents an additional modality for achieving myocardial protection.

Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection

BACKGROUNDnMitochondrial and sarcolemmal ATP-sensitive potassium channels have been implicated in cardioprotection; however, the role of these channels in magnesium-supplemented potassium (K/Mg) cardioplegia during ischemia or reperfusion is unknown.nnnMETHODSnRabbit hearts (n = 76) were used for Langendorff perfusion. Sham hearts were perfused for 180 minutes. Global ischemia hearts received 30 minutes of global ischemia and 120 minutes of reperfusion. K/Mg hearts received cardioplegia before ischemia. The role of ATP-sensitive potassium channels in K/Mg cardioprotection during ischemia and reperfusion was investigated, separately using the selective mitochondrial ATP sensitive potassium and channel blocker, 5-hydroxydecanoate, and the selective sarcolemmal ATP-sensitive potassium channel blocker HMR1883. Separate studies were performed using the selective mitochondrial ATP-sensitive potassium channel opener, diazoxide, and the nonselective ATP-sensitive potassium channel opener pinacidil.nnnRESULTSnInfarct size was 1.9%+/-0.4% in sham, 3.7%+/-0.5% in K/Mg, and 27.8%+/-2.4% in global ischemia hearts (p < 0.05 versus K/Mg). Left ventricular peak-developed pressure (percent of equilibrium) at the end of 120 minutes of reperfusion was 91%+/-6% in sham, 92% +/-2% in K/Mg, and 47%+/-6% in global ischemia (p < 0.05 versus K/Mg). Blockade of sarcolemmal ATP-sensitive potassium channels in K/Mg hearts had no effect on infarct size or left ventricular peak-developed pressure. However, blockade of mitochondrial ATP-sensitive potassium channels before ischemia significantly increased infarct size to 23%+/-2% in K/Mg hearts (p < 0.05 versus K/Mg; no statistical significance [NS] as compared to global ischemia) and significantly decreased left ventricular peak-developed pressure to 69%+/-4% (p < 0.05 versus K/Mg). Diazoxide when added to K/Mg cardioplegia significantly decreased infarct size to 1.5%+/-0.4% (p < 0.05 versus K/Mg).nnnCONCLUSIONSnThe cardioprotection afforded by K/Mg cardioplegia is modulated by mitochondrial ATP-sensitive potassium channels. Diazoxide when added to K/Mg cardioplegia significantly reduces infarct size, suggesting that the opening of mitochondrial ATP-sensitive potassium channels with K/Mg cardioplegic protection would allow for enhanced myocardial protection in cardiac operations.

Adenosine-enhanced ischemic preconditioning modulates necrosis and apoptosis: effects of stunning and ischemia–reperfusion

BACKGROUNDnAdenosine-enhanced ischemic preconditioning extends the protection of ischemic preconditioning by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery.nnnMETHODSnThe effects of adenosine-enhanced ischemic preconditioning on necrosis and apoptosis were investigated in the sheep heart using models of stunning (15 minutes regional ischemia, 120 minutes reperfusion) and ischemia-reperfusion (30 and 60 minutes regional ischemia, 120 minutes reperfusion). Ischemic preconditioned hearts received 5 minutes regional ischemia, 5 minutes reperfusion before ischemia. Adenosine-enhanced ischemic preconditioned hearts received a 10 mmol/L adenosine bolus (10 mL) through the left atrium coincident with ischemic preconditioning. Adenosine hearts received a 10 mmol/L bolus (10 mL) of adenosine. Regional ischemic hearts received no pretreatment.nnnRESULTSnMinimal apoptosis (< 45 per 3,000 myocytes) was observed in the stunning models but was significantly increased with ischemia-reperfusion in regional ischemic hearts after 30 minutes (p < 0.05 versus ischemic preconditioning, adenosine, or adenosine-enhanced ischemic preconditioning) and in adenosine and ischemic preconditioned hearts after 60 minutes ischemia (p < 0.05 versus adenosine-enhanced ischemic preconditioning). DNA laddering was apparent after 60 minutes ischemia in regional ischemia, adenosine, and ischemic preconditioning but not in adenosine-enhanced ischemic preconditioned hearts.nnnCONCLUSIONSnAdenosine-enhanced ischemic preconditioning significantly ameliorates necrosis and apoptosis in the regional ischemic blood-perfused heart.

Impact of mold infections in explanted lungs on outcomes of lung transplantation.

Introduction. Little is known about the incidence or significance of mold infections in the explanted lungs of lung transplant recipients. Method. We reviewed the histopathology of the explanted lungs from 304 patients who underwent lung transplantation at our institution from 2005 to 2007 and received alemtuzumab induction therapy and posttransplant voriconazole prophylaxis. Results. Invasive mold infections were present in the explanted lungs of 5% (14 of 304) of patients, including chronic necrotizing pneumonias (n=7), mycetomas (n=4), and invasive fungal pneumonias (n=3). Only 21% (3 of 14) received immunosuppressive therapy within 1 year before lung transplantation, suggesting that lung damage itself predisposed patients to mold infections. The risk of mold infection was higher in patients with cystic fibrosis (11%, 4 of 35) than other underlying lung diseases (4%, 10 of 269). Pulmonary mold infections were not diagnosed or suspected in 57% (8 of 14) of patients. Despite secondary voriconazole prophylaxis, fungal infections developed in 43% (6 of 14) of patients with mold infections of the explanted lungs compared with 14% (42 of 290) of patients without mold infections (P=0.01). Three patients developed invasive fungal infections while on voriconazole prophylaxis and three developed fungal infections more than 8 months after the discontinuation of voriconazole. The mortality attributable to invasive fungal infections among patients with mold infections of the explanted lungs was 29% (4 of 14). Conclusion. Invasive mold infections in the explanted lungs are often not recognized before lung transplantation and are associated with poor outcomes.

Surgical treatment for transvenous tumor extension into the heart: Four cases

From 1984 to 1996, four patients with transvenous intracardiac tumor extension underwent operations in the Kobe University Hospital. The primary tumors of two were intravenous leiomyomatoses originating from the uterus; a third patient had invasive thymoma, and the fourth patient had clear cell sarcoma of the kidney. In 1985, one patient had a curative, staged resection. One-stage operations were carried out in three patients, and all intracardiac tumors were successfully resected en bloc with the primary tumors under conditions of electrical ventricular fibrillation and mild hypothermia. Combined venous reconstructions were necessary for en bloc resection in three cases. Two patients with malignancy received postoperative chemoradiotherapy, and all four patients were discharged uneventfully from our hospital. We consider radical resection with curative intent only for patients with tumors extending into the heart. In these cases, a one-stage operation is preferable, and electrical ventricular fibrillation with mild hypothermia is a recommended method of circulatory assist because of its simplicity.

Obese patients and mechanical circulatory support: weight loss, adverse events, and outcomes.

BACKGROUNDnObesity and heart failure are increasingly common, but the outcomes, weight changes, and adverse events of patients with advanced heart failure and obesity on mechanical support is not well described.nnnMETHODSnWe retrospectively reviewed all non-underweight patients with durable mechanical support at a single institution from January 2000 until December 2008 and compared outcomes, weight change, and Interagency Registry for Mechanically Assisted Circulatory Support-defined adverse events between obese and nonobese patients.nnnRESULTSnA total of 169 patients were included; 113 (67%) nonobese and 56 (33%) obese. Baseline characteristics, pump types, and implant duration were similar for both populations with the exception of more diabetes (61% vs 26%, p < 0.0001) and hypertension (61% vs 42%, p = 0.019) in the obese. Outcomes on mechanical support at 6 months were not different between groups. There was no significant difference between the nonobese and obese groups in the change in body mass index (-0.3 vs -1.0 mg/m(2), p = 0.29) over the duration of support. Obese patients, as compared with the nonobese, had higher incidence rates of sepsis (64.5% vs 34.7%, respectively, p = 0.006) and reoperation for infectious complications (34.2% vs 13.3%, respectively, p = 0.014). Obese patients also had a higher cumulative incidence of sepsis and reoperation for infection. Two-year posttransplant outcomes were not different in the obese and nonobese.nnnCONCLUSIONSnObese patients have similar outcomes on mechanical support, but at the cost of a higher cumulative incidence of sepsis and reoperations for infection; however, obese patients lose little weight while on mechanical support.

Donor smoking history and age in lung transplantation: a revisit.

Background When selecting a donor for lung transplantation, it is generally believed that the best outcomes occur when the donor has no smoking history. Because we experienced unexpected adverse outcomes after transplant of lungs from teenaged donors with no smoking history, this study revisited the effects of donor smoking history in relation to age on transplant outcomes. Methods We conducted a retrospective review of 532 consecutive lung transplants performed at our institution. Most donors (293, 55%) had a history of smoking; 239 donors were nonsmokers. The smoking donors were further subgrouped based on consumption (<20, 20–40, or >40 pack-years). The nonsmoking donors were subgrouped by age (<20 years or ≥20 years). Recipients’ characteristics and outcomes were compared. Results The recipients of lungs from donors with a smoking history showed better 5-year survival than recipients of lungs from nonsmokers (65.8% vs. 48.3%, P<0.05), but recipients of lungs from heavy smokers (>40 pack-years smoking history) exhibited a significantly higher incidence of severe primary graft dysfunction and higher short- and long-term mortality than the recipients of lungs from donors who smoked less. Surprisingly, recipients of lungs from teenaged donors with no smoking history exhibited a higher morbidity and mortality than recipients of lungs from adult nonsmoking donors but did not exhibit decreased posttransplant forced expiratory volume in 1 sec. Conclusions In this large, single-center experience, the absence of smoking history in the donor did not result in better long-term outcomes after lung transplantation. Potential problems with lungs from teenaged donors with no smoking history were suggested.

Effects of NHE-1 inhibition on cardioprotection and impact on protection by K/Mg cardioplegia

BACKGROUNDnCardiac sodium hydrogen exchanger isoform-1 (NHE-1) activity during ischemia/reperfusion contributes to myocardial injury. The effects of NHE-1 inhibition during ischemia or reperfusion and on the protection afforded by K/Mg cardioplegia was unknown.nnnMETHODSnRabbit hearts were used for Langendorff perfusion. Control hearts were perfused for 180 minutes. Global ischemia (GI) hearts received 30 minutes normothermic global ischemia and 120 minutes reperfusion. K/Mg hearts received cardioplegia 5 minutes before ischemia. Separate groups of GI and K/Mg hearts received the NHE-1 inhibitor, HOE-642, before ischemia (HOE-642-I), at the immediate start of reperfusion (HOE-642-R), or both before ischemia and at the immediate start of reperfusion (HOE-642-IR).nnnRESULTSnLeft ventricular peak developed pressure was significantly increased in HOE-I, HOE-R, and HOE-IR throughout reperfusion (p < 0.05 versus GI). Infarct size was significantly decreased (p < 0.05 versus GI) in all groups, but was significantly increased in HOE-R as compared with HOE-IR (p < 0.05). NHE-1 inhibition with K/Mg cardioplegia significantly decreased left ventricular peak developed pressure after 90 minutes of reperfusion (p < 0.05 versus K/Mg), with no significant effect on infarct size.nnnCONCLUSIONSnNHE-1 inhibition used alone provides cardioprotection with optimal effects being observed with HOE-IR. NHE-1 inhibition with K/Mg cardioplegia decreases postischemic functional recovery during late reperfusion.