Shigeyuki Ozaki

Hemodynamic changes and right heart support during vertical displacement of the beating heart

BACKGROUND Hemodynamic instability during heart displacement in off-pump multivessel coronary artery bypass grafting might be related to right heart dysfunction. The Enabler (HemoDynamics Systems Ltd, Upper Yoqneam, Israel) is a cannula pump that expels blood from the right atrium into the pulmonary artery. We studied the hemodynamic changes and the role of the enabler during heart displacement. METHODS Nine anesthetized sheep were assessed for hemodynamic changes during 90-degree heart displacement with or without Enabler support. Hemodynamic parameters included cardiac output, systemic arterial blood pressures, and left and right heart filling pressures. RESULTS Heart displacement caused a significant decrease in cardiac output and systemic blood pressure (46%+/-5%, p = 0.001; and 20%+/-5%, p = 0.009, respectively), with a concomitant 137%+/-24% (p = 0.003) increase in central venous pressure. No significant change in left atrial pressure was observed. Activation of the Enabler caused a significant increase in cardiac output and systemic blood pressure (67%+/-15%, p = 0.01; and 17%+/-7%, p = 0.04, respectively), as well as a decrease in central venous pressure by 49%+/-8% (p = 0.0001). CONCLUSIONS Heart displacement causes hemodynamic instability mainly by right heart dysfunction. The Enabler significantly stabilized circulation during vertical displacement of the beating heart.

Remote preconditioning lessens the deterioration of pulmonary function after repeated coronary artery occlusion and reperfusion in sheep

PurposeWe investigated whether remote organ preconditioning (RPC) can preserve pulmonary function following repeated myocardial ischemia/reperfusion in a model mimicking multi-vessel off-pump coronary artery bypass (OPCAB) revascularization.MethodsNine sheep (Group-RPC) underwent RPC by three episodes of five-minute occlusion and five-minute reperfusion of the iliac artery. Five sheep (Group-C) were time-matched controls. Afterwards, ten-minute occlusion and reperfusion of the left anterior descending, the first diagonal and the left circumflex coronary arteries were performed consecutively. Hemodynamic and respiratory parameters and arterial blood gases were measured until 120 min after the final coronary reperfusion. Anesthesia was maintained with halothane in oxygen and nitrous oxide. Animals were ventilated with a tidal volume of 15–20 mL·kg−1 in a non-rebreathing system, and a respiratory rate 14–16 min, with 5-cm H2O positive end expiratory pressure after thoracotomy.ResultsRepeated coronary occlusion and reperfusion was associated in this experimental model with an increase in pulmonary vascular resistance (PVR) and pulmonary arterial pressure (PAP) and a decrease in PaO2 and PaO2/FlO2 in Group-C. After 120 min reperfusion, PaO2 and PaO2/FlO2 in Group-RPC were higher ( 192 ± 69 mmHg and 241 ± 78vs I 15 ± 54 mmHg and 129 ± 64,P < 0.05), while PVR and PAP were lower than in Group-C. At 120 min of reperfusion, PaO2 and PaO2/FlO2 were inversely correlated with PVR(P < 0.01).ConclusionsRPC by transient occlusion of the iliac artery improves lung gas exchange after repeated coronary artery occlusion and reperfusion mimicking OPCAB surgery, and preserves low PVR in sheep.RésuméObjectifNous avons vérifié si ie préconditionnement éioigné d’un organe (PEO) peut préserver ia fonction puimonaire à ia suite d’ischémie/reperfusion myocardique répétée chez un modèie imitant la revascuiarisation d’un pontage aortocoronarien plurivasculaire à cœur battant (PACCB)MéthodeNeuf moutons (Groupe PEO) ont subi un PEO en trois épisodes d’occlusion de cinq minutes suivis de reperfusion de cinq minutes de l’artère iliaque. Cinq moutons (Groupe T) ont constitué le groupe témoin apparié dans le temps. Par la suite, nous avons réalisé successivement l’occlusion et la reperfusion, en dix minutes, des artères coronaires interventriculaire antérieure, première diagonale et circonflexe. Les paramètres hémodynamiques et respiratoires et la gazométrie du sang artériel ont été mesurés jusqu’à 120 min après la reperfusion coronaire finale. L’anesthésie a été maintenue avec de l’halothane dans un mélange d’oxygène et de protoxyde d’azote. Les animaux ont été ventilés selon un volume de 15- 20 mL·kg−1 avec un système sans réinspiration, et une fréquence respiratoire de 14–16 min selon une pression positive en fin d’expiration de 5 cm de H2O après la thoracotomie.RésultatsDans ce modèle expérimental, l’occlusion et la reperfusion coronaires répétées ont été associées à une augmentation de la résistance vasculaire pulmonaire (RVP) et de la tension artérielle pulmonaire (TAP) ainsi qu’à une baisse de la PaO2 et de la PaO2/ElO2 dans le Groupe T. Dans le Groupe PEO, après 120 min de reperfusion, la PaO2 et la PaO2/FIO2 étaient plus élevées (192 ± 69 mmHg et 241 ± 78 vs 115 ± 54 mmHg et 129 ± 64, P < 0,05), tandis que la RVP et la TAP étaient plus faibles que dans le Groupe T.À 120 min de reperfusion, la PaO2 et la PaO2/FlO2 étaient en corrélation inverse avec la RVP(P < 0,01).ConclusionLe PEO par occlusion transitoire de l’artère iliaque améliore les échanges gazeux pulmonaires après l’occlusion et la reperfusion répétée de l’artère coronaire simulant un PACCB et il maintien une faible RVP.

Calcification characteristics of porcine stentless valves in juvenile sheep

OBJECTIVE To compare calcification characteristics of two porcine stentless valves (Toronto SPV and Freestyle) with different designs, fixation and antimineralization techniques using a juvenile sheep model of valve implantation inside the circulation. METHODS The stentless valves (n = 2 x 6) were implanted in juvenile sheep in the pulmonary artery as an interposition, while the circulation was maintained with a right ventricular assist device. The model was validated by the implantation of, clinically well-known, porcine (Hancock II) and pericardial (Pericarbon) valves. Half of the valves were explanted after 3 months, the rest after 6 months. Valves were examined macroscopically, by X-ray, light microscopy (HE, Masson, Von Giesson, Von Kossa, PTAH stains), and transmission electron microscopy. Quantitative determination of the calcium content of the cusps was performed with atomic absorption spectrometry. RESULTS After 3 months, the Freestyle had an extensively calcified aortic wall, most prominent at the outflow side of the porcine valve. After 6 months, calcification increased transmurally, but the valve cusps were free of calcification, and the inflow side was only slightly calcified. The Toronto SPV valve also started to calcify at the inflow side of the valve after 3 months with increased calcification after 6 months. The base of the Toronto SPV valve cusps showed slight calcification after 6 months of implantation. CONCLUSIONS The pattern of calcification of the porcine aortic wall differs between the two studied stentless valves, with calcification located predominantly at the outflow side in the Freestyle valve, but also at the inflow side in the Toronto SPV valve. The cusps of the Freestyle valve were less prone to calcification than those from the Toronto SPV valve.

THE ENABLER CANNULA PUMP : A NOVEL CIRCULATORY SUPPORT SYSTEM

Background The enabler circulatory support system is a catheter pump which expels blood from the left or right ventricular cavity and provides pulsatile flow in the ascending aorta or pulmonary artery. It is driven by a bedside installed pulsatile driving console. The device can easily be implanted by a minimal invasive approach, similar to the Hemopump. Purpose To demonstrate the hemodynamic performance of this new intracardiac support system. Methods In a series of 9 sheep, hemodynamic evolutions were recorded in various conditions of myocardial contractility (the non-failing, the moderately failing and the severely failing heart). Heart failure was induced by injection of microspheres in the coronary arteries. Results Introduction of the cannula through the aortic valve was feasible in all cases. Pump flow by the enabler was gradually increased to a maximum of 3.5 L/min. Diastolic (and mean) aortic blood pressure is significantly increased in the non-failing and moderately failing condition (counterpulsation mode). In heart failure, cardiac output is significantly increased by the pump (p<0.0001). A drop in left atrial pressure (indicating unloading) is achieved in all conditions but reaches significant levels only during heart failure (p=0.0068). Conclusions This new circulatory support system contributes to stabilization of the circulation in the presence of cardiac unloading. In heart failure it actually supports the circulation by increasing cardiac output and perfusion pressure.

Thickened intima of the aortic arch is a risk factor for stroke with coronary artery bypass grafting

BACKGROUND Perioperative stroke is one of the most serious complications of cardiac surgery. METHODS Using transesophageal echocardiography, we estimated the intimal thickness of the thoracic aorta as an index of the severity of aortic atherosclerosis to determine the risk of stroke in coronary artery bypass grafting (CABG) patients. The study population comprised 315 consecutive patients who underwent isolated CABG with cardiopulmonary bypass. RESULTS Five patients (1.6%) had perioperative cerebral stroke or systemic emboli. We compared the mean intimal thicknesses of the ascending aorta, aortic arch, and descending aorta. Mean thicknesses in patients without stroke were 2.07 +/- 0.76, 2.78 +/- 1.15, and 2.32 +/- 1.21 mm, respectively, and mean thicknesses in the stroke patients were 1.94 +/- 0.55, 6.94 +/- 3.79, and 3.39 +/- 1.85 mm, respectively. The patients with an intima of more than 5 mm at the aortic arch had a significantly greater incidence of perioperative stroke (p = 0.007). CONCLUSIONS These results suggest that patients who have an aortic arch intima thickened to more than 5 mm are at a significantly high risk for perioperative stroke, and thus, the CABG procedure should be carefully evaluated to prevent such complications.

Calcification Characteristics of Porcine Stented Valves in a Juvenile Sheep Model

BACKGROUND Different antimineralization treatments of stented porcine bioprostheses were evaluated: ethanol (Epic), alpha-amino-oleic acid (AOA) (Mosaic), and sodium dodecyl sulfate (SDS) (Hancock II). A nontreated, glutaraldehyde-fixed valve (Labcor) served as control. METHODS For each treatment, six valves were implanted in juvenile sheep in the pulmonary position. Valves were explanted after 3 and 6 months and examined macroscopically, by roentgenogram and light and transmission electron microscopy. Calcium content (microg/mg) was determined by atomic absorption spectrometry. RESULTS The Labcor valves revealed small calcium deposits in the cusps, although calcium content remained low (median value 0.4+/-0.8 microg/mg). SDS did not prevent cusp calcification as assessed by histology and calcium content measurement, which was higher than in all other valves: 1.9+/-4.6 microg/mg (p < 0.05). Cusp retraction and rupture were occasionally found in the Hancock. The Mosaic and Epic valves showed no cusp calcification and had low calcium contents (0.3+/-2.4 microg/mg and 0.7+/-0.6 microg/mg, respectively). Epic showed less pannus formation, but had hematoma or iron staining in the cusps. CONCLUSIONS SDS is inefficient as an antimineralization treatment, in contrast to ethanol or AOA. Cusp hematoma after ethanol treatment needs further investigation.

Effect of transmyocardial laser revascularization on chronic ischemic hearts in sheep.

BACKGROUND We investigated the effect of transmyocardial laser revascularization (TMR) on myocardial function and regional blood flow in an animal model of ischemic heart disease. METHODS Chronic ischemia was induced in 11 sheep by the application of coronary stenosis on the left anterior descending (LAD) and circumflex coronary artery (LCX). Ten weeks later, in six of them, transmyocardial channels were created in the anterior free wall and in the posterior wall of the left ventricle. Five animals served as controls. The myocardial function was assessed by echocardiography taken at baseline and every 2 weeks after coronary stenosis and after TMR. Myocardial perfusion was measured by colored microspheres, injected at baseline, immediately after coronary stenosis, before and after TMR, and at 20 weeks after coronary stenosis. The hearts were retrieved at 20 weeks for light microscopic examination. RESULTS The left ventricular end-diastolic and end-systolic cavity area was elevated 20 weeks after coronary stenosis in the control and TMR groups. There was no difference between groups (analysis of variance; ANOVA, non-significant). The wall thickening fraction (WTF) decreased progressively and significantly after coronary stenosis in both groups. The WTF was further acutely reduced by TMR, and recovered gradually to the pre-TMR level. No significant difference in WTF was observed between the TMR and control groups. The resting myocardial blood flow was significantly increased by TMR at 20 weeks (P=0.03). Light microscopic examination revealed channel patency in 49% of the laser scars at 10 weeks post-TMR. A dense capillary network was observed at the edges of the surrounding scar. CONCLUSIONS In an experimental model of ischemic heart disease, TMR developed angiogenesis in the lased channels, but, however, failed to improve myocardial function.

The intra-aortic cannula pump: A novel assist device for the acutely failing heart

OBJECTIVE The intra-aortic cannula pump is a catheter pump designed to support the acutely failing heart. It expels blood from the left ventricle into the ascending aorta in a pulsatile flow pattern. The aim of the study was to analyze the hemodynamic performance of this new intracardiac support system in acute heart failure. METHODS A 24F cannula was studied in a series of 16 sheep. Hemodynamic changes were assessed in the nonfailing, the moderately failing, and the severely failing heart. Heart failure was induced by an injection of microspheres into the left anterior descending coronary artery. The cannula was inserted through the aortic arch and introduced through the aortic valve into the left ventricle. RESULTS Cannula insertion was feasible in all animals. Flow through the intra-aortic cannula flow was increased to a maximum of 3 L/min. No hemodynamic changes were observed in the nonfailing heart. A significant increase in cardiac output was observed in the moderately and severely reduced left ventricle (2.67 +/- 0.7 L to 3.51 +/- 0.83 L; P =.001; and 1.18 +/- 0.77 L to 2.43 +/- 0.44 L; P =.001, respectively). A drop in left atrial pressure was achieved in moderate and severe heart failure (14.1 +/- 5.93 mm Hg to 9.71 +/- 2.63 mm Hg; P =.0001; and 23 +/- 7.16 mm Hg to 11.2 +/- 2.55 mm Hg; P = 0.0001, respectively). Systolic and diastolic systemic blood pressures increased in the severely failing heart (57.3 +/- 12.8 mm Hg to 75.4 +/- 11.2 mm Hg; P =.0001; and 35.6 +/- 8.2 mm Hg to 60 +/- 14.3 mm Hg; P =.0006, respectively). CONCLUSIONS Hemodynamic data demonstrate the beneficial effects of the intra-aortic cannula pump in moderate and severe heart failure. The intra-aortic cannula pump represents a new modality for the treatment of acute heart failure.

Inhibition of neointimal proliferation in balloon-injured arteries using non-anticoagulant heparin-carrying polystyrene.

Non-anticoagulant heparin-carrying polystyrene (NAC-HCPS) has a higher activity to inhibit proliferation and migration of smooth muscle cells (SMCs) than heparin (Hep), periodate-oxidized (IO4-) Hep, and periodate-oxidized alkaline-degraded low molecular weight (IO4-LMW-) Hep. Less than 10 &mgr;g/ml of NAC-HCPS significantly inhibited the proliferation and migration of SMCs in vitro, while over 10-fold higher concentrations of Hep, IO4-Hep, and IO4-LMW-Hep were required to obtain the same inhibition. On the other hand, neointimal growth (intimal cross-section area and intimal cross-section area/medial cross-section area ratio) in vivo following vascular injury 28 days after balloon denudation in a rat carotid artery was substantially inhibited with high dose of intravenous administration (total 30 mg) of respectively IO4-Hep, IO4-LMW-Hep, and NAC-HCPS. A low-dose (total 10 mg) administration of IO4-Hep and IO4-LMW-Hep did not prevent the neointimal growth when compared with the control; only NAC-HCPS (total 10 mg) was able to significantly inhibit the neointimal. Thus, NAC-HCPS has a more-than 10-fold larger activity to inhibit SMC activities such as proliferation and migration in vitro, when comparing with Hep, IO4-Hep, and IO4-LMW-Hep; NAC-HCPS also prevents neointimal growth in vivo at lower doses.

Modified stentless porcine valve enhances accelerated cuspal calcification in the juvenile sheep model

OBJECTIVE Stent mounting of any bioprosthesis, induces a loss of mobility and reduces the effective valve orifice. By contrast, for stentless procedures, the higher surgical technicality remains a major obstacle for many surgeons. In an attempt to facilitate the insertion of the stentless porcine aortic valve (Toronto SPV), we tried to alter the design by lowering the invasive profile at the depth of the sinuses on both coronary sites. This could theoretically facilitate the implant of the modified stentless valve with an easygoing single layer suture at the challenging subcoronary level and make it more attractive for every surgeon. METHODS Modifications of the standard model were done by lowering the profile at the depth of the sinuses on both coronary sites, whether by plication or excision of the protruding porcine aortic wall at the nadir of each coronary sinus. Nine juvenile sheep underwent implantation of stentless porcine aortic valves in pulmonary position: 3 standard Toronto SPV, 3 plicated Toronto SPV and 3 excised Toronto SPV. In each series, valves were explanted after 3 months. Valves were analyzed. RESULTS The cusps of standard Toronto SPV were perfectly functioning and pliable, without visible calcification after three months. The calcium content of the cusps was less than those in the plicated and excised Toronto SPV (2.4 +/- 0.7 microg/mg versus 10.8 +/- 5.9 and 6.7 +/- 3.4 microg/mg). In the plicated and excised valves, calcification of the cusp was more pronounced in the commissural region (3.9 +/- 1.9, 29.0 +/- 16.7, 13.8 +/- 9.5 microg/mg in the standard, plicated and excised Toronto SPV, respectively). On the other hand, the aortic wall from the plicated Toronto SPV had more calcium than that from the other groups (53.6 +/- 6.3, 41.2 +/- 7.1, 45.2 +/- 7.4 microg/mg in the plicated, standard and excised Toronto SPV, respectively). CONCLUSIONS The modification of stentless porcine valve enhanced accelerated cuspal calcification in the commissural region. It accentuated that the correct implantation technique for stentless procedures is extremely important in order to prevent early degeneration.