Takafumi Masai

Effects of perfusion mode on regional and global organ blood flow in a neonatal piglet model

BACKGROUND Organ injury (brain, kidney, and heart) has been reported in up to 30% of pediatric open heart surgery patients after conventional hypothermic non-pulsatile cardiopulmonary bypass (CPB) support with or without deep hypothermic circulatory arrest (DHCA). The effects of pulsatile (with a Food and Drug Administration approved modified roller pump) versus non-pulsatile perfusion on regional and global cerebral, renal, and myocardial blood flow were investigated during and after CPB with 60 minutes of DHCA in a neonatal piglet model. METHODS Piglets, mean weight 3 kg, were used in both pulsatile (n = 7) and non-pulsatile (n = 7) groups. After initiation of CPB, all animals were subjected to hypothermia for 25 minutes, reducing the rectal temperatures to 18 degrees C, 60 minutes of DHCA followed by 10 minutes of cold reperfusion and 40 minutes of rewarming with a pump flow of 150 mL/kg/min. During cooling and rewarming, alpha-stat acid-base management was used. Differently labeled radioactive microspheres were injected pre-CPB, on normothermic CPB, pre-DHCA, post-DHCA, and after CPB to measure the regional and global cerebral, renal, and myocardial blood flows. RESULTS Global cerebral blood flow was significantly higher in the pulsatile group compared to the non-pulsatile group at normothermic CPB (100.4 +/- 6.3 mL/100 gm/min versus 70.2 +/- 8.1 mL/100 gm/min, p < 0.05) and pre-DHCA (77.2 +/- 5.2 mL/100 gm/min versus 56.1 +/- 6.7 mL/100 gm/min, p < 0.05). Blood flow in cerebellum, basal ganglia, brain stem, and right and left cerebral hemispheres had an identical pattern with the global cerebral blood flow. Renal blood flow appeared higher in the pulsatile group compared to the non-pulsatile group during CPB, but the results were statistically significant only at post-CPB (94.8 +/- 9 mL/100 gm/min versus 22.5 +/- 22 mL/100 gm/min, p < 0.05). Pulsatile flow better maintained the myocardial blood flow compared to the non-pulsatile flow after CPB (316.6 +/- 45.5 mL/100 gm/min versus 188.2 +/- 19.5 mL/100 gm/min, p < 0.05). CONCLUSIONS Pulsatile perfusion provides superior vital organ blood flow compared to non-pulsatile perfusion in this model.

Pulsatile and nonpulsatile flows can be quantified in terms of energy equivalent pressure during cardiopulmonary bypass for direct comparisons.

The purpose of this study was to quantify and compare pulsatile and nonpulsatile pressure and flow waveforms in terms of energy equivalent pressure (EEP) during cardiopulmonary bypass in a neonatal piglet model. EEP is the ratio of the area under the hemodynamic power curve and the flow curve. Piglets, mean weight of 3 kg, were used in physiologic pulsatile pump (n = 7), pulsatile roller pump (n = 6), and nonpulsatile roller pump (n = 7) groups. Data (waveforms of the femoral artery pressure, pump flow, and preaortic cannula extracorporeal circuit pressure) were collected during normothermic cardiopulmonary bypass at 35 degrees C (15 minutes on-pump), before deep hypothermic circulatory arrest (pre-DHCA) at 18 degrees C, and after cold reperfusion and rewarming (post-DHCA) at 36 degrees C. The pump flow rate was 150 ml/kg/min in all three groups. During pulsatile perfusion, the pump rate was 150 bpm in both pulsatile groups. Although there was no difference in mean pressures in all groups, EEP and the percentage increase of pressure (from mean pressure to EEP) of mean arterial pressure and preaortic cannula extracorporeal circuit pressure were higher with pulsatile perfusion compared with nonpulsatile perfusion (p < 0.001). In particular, the physiologic pulsatile pump group produced significantly higher hemodynamic energy compared with the other groups (p < 0.001). These results suggest that pulsatile and nonpulsatile flows can be quantified in terms of EEP for direct comparisons, and pulsatile flow generates higher energy, which may be beneficial for vital organ perfusion during cardiopulmonary bypass.

Hepatic dysfunction after left ventricular mechanical assist in patients with end-stage heart failure: role of inflammatory response and hepatic microcirculation

BACKGROUND In the condition of preexisting vital organ failure induced by heart failure, hepatic failure often progresses despite establishment of adequate hemodynamic support through a left ventricular assist device (LVAD) and results in a high mortality rate. We hypothesized that inflammatory responses, including those induced by infection and their influence on organ perfusion, may contribute to the pathogenesis of this progressive hepatic failure and subsequent multiple organ failure as reported in the current investigation on multiple organ failure after major surgery or trauma. METHODS Hepatic function and its relation to inflammatory response and hepatic microcirculation were evaluated in 16 consecutive patients who received an implantation of LVAD for end-stage cardiomyopathy, between 1992 and 2000. Patients were divided into two groups: 5 patients who died from multiple organ failure after severe hepatic failure (group 1) and 11 patients who did not develop severe hepatic failure (group 2). Serum levels of CRP, interleukin (IL)-6, IL-8, and serum hyaluronan, a known indicator of hepatic sinusoidal function, were measured pre- and postoperatively in both groups. RESULTS Serum ALT and AST levels during LVAD support were similar in the two groups. Serum total bilirubin (T-Bil), CRP, IL-6, and IL-8 levels before and during the first 20 days of LVAD support were significantly higher in group 1 than those in group 2 (p < 0.01 to 0.05). Serum hyaluronan levels in both groups were significantly correlated with T-Bil levels (r = 0.60, p < 0.05 in group 1; r = 0.68, p < 0.0001 in group 2). Histopathological examination by transvenous liver biopsy in a group 1 patient showed hepatic sinusoidal damage as well as cholestasis and fibrosis. CONCLUSIONS Patients with hyperbilirubinemia and inflammatory reactions before LVAD support showed increased hyperbilirubinemia and inflammatory cytokine and hyarulonan levels despite adequate hemodynamics achieved under LVAD support. These results suggest that inflammatory response contributes to subsequent aggravation of hepatic dysfunction, probably with underlying and continuing derangement in hepatic sinusoidal microcirculation even under systemic circulatory support.

Pulsatile perfusion improves regional myocardial blood flow during and after hypothermic cardiopulmonary bypass in a neonatal piglet model.

Pediatric myocardial related morbidity and mortality after cardiopulmonary bypass (CPB) are well documented, but the effects of pulsatile perfusion (PP) versus nonpulsatile perfusion (NPP) on myocardial blood flow during and after hypothermic CPB are unclear. After investigating the effects of PP versus NPP on myocardial flow during and after hypothermic CPB, we quantified PP and NPP pressure and flow waveforms in terms of the energy equivalent pressure (EEP) for direct comparison. Ten piglets underwent PP (n = 5) or NPP (n = 5). After initiation of CPB, all animals underwent 15 minutes of core cooling (25 degrees C), 60 minutes of hypothermic CPB with aortic cross-clamping, 10 minutes of cold reperfusion, and 30 minutes of rewarming. During CPB, the mean arterial pressure (MAP) and pump flow rates were 40 mm Hg and 150 ml/kg per min, respectively. Regional flows were measured with radiolabeled microspheres. During normothermic CPB, left ventricular flow was higher in the PP than the NPP group (202+/-25 vs. 122+/-20 ml/l 00 g per min). During hypothermic CPB, no significant intragroup differences were observed. After 60 minutes of ischemia and after rewarming (276+/-48 vs. 140+/-12 ml/100 g per min; p < 0.05) and after CPB (271+/-10 vs. 130+/-14 ml/100 g per min; p < 0.05), left ventricular flow was higher in the PP group. Right ventricular flow resembled left ventricular flow. The pressure increase (from MAP to EEP) was 10+/-2% with PP and 1% with NPP (p < 0.0001). The increase in extracorporeal circuit pressure (ECCP) (from ECCP to EEP) was 33+/-10% with PP and 3% with NPP (p < 0.0001). Pulsatile flow generates significantly higher energy, enhancing myocardial flow during and after hypothermic CPB and after 60 minutes of ischemia in this model.

Mycotic aneurysm of the infrarenal abdominal aorta infected by Clostridium septicum: A case report of surgical management and review of the literature

We report a surgical case of mycotic aneurysm of the infrarenal abdominal aorta infected by Clostridium septicum. The patient was first treated with an in situ prosthetic graft replacement. When the infection recurred 5 weeks after the aortic surgery, the patient was successfully treated by transposition of rectus abdominis muscle flap around the graft. Only 19 cases of mycotic aneurysm or aortic dissection caused by Clostridium septicum have been reported. Ten of 12 patients who underwent vascular surgery survived, whereas all 7 patients who did not undergo surgery died. Surgical treatment should be undertaken since the surgical results seem satisfactory.

Effect of Cardiopulmonary Bypass Under Tepid Temperature on Inflammatory Reactions

BACKGROUND Cardiopulmonary bypass (CPB) causes inflammatory reactions and abnormal responses of vascular resistance. Theoretically, the difference in the blood temperature during CPB may influence the degree of CPB-induced inflammatory reactions. METHODS To elucidate the effect of the perfusate temperature during CPB, serum levels of inflammatory cytokines, neutrophil elastase, complements, and vasoactive substances were measured in 18 patients undergoing elective coronary artery bypass grafting under tepid temperature (34 degrees C) and moderate hypothermia (28 degrees C). Respiratory index and systemic vascular resistance index during and after CPB and intubation time after postoperative course were also analyzed. RESULTS The patterns of the change in interleukin-8 and neutrophil elastase were significantly different between the two groups. The tepid group showed an earlier decrease in interleukin-8 and neutrophil elastase levels as compared with the hypothermic group. The prostaglandin E2 level just after CPB was significantly higher in the tepid group than in the hypothermic group. Systemic vascular resistance index and respiratory index and intubation time were significantly lower in the tepid group than in the hypothermic group. CONCLUSIONS These results demonstrated that tepid CPB affected the inflammatory cytokine release and neutrophil activation compared with hypothermic CPB, resulting in the attenuation of respiratory dysfunction. This may suggest a beneficial effect of tepid temperature in CPB with possible attenuation of the postperfusion syndrome.

Precise Quantification of Pulsatility is a Necessity for Direct Comparisons of Six Different Pediatric Heart-lung Machines in a Neonatal Cpb Model

Generation of pulsatile flow depends on an energy gradient. Surplus hemodynamic energy (SHE) is the extra hemodynamic energy generated by a pulsatile device when the adequate pulsatility is achieved. The objective of this study was to precisely quantify and compare pressure-flow waveforms in terms of surplus hemodynamic energy levels of six different pediatric heart-lung machines in a neonatal piglet model during cardiopulmonary bypass (CPB) procedures with deep hypothermic circulatory arrest (DHCA). Thirty-nine piglets (average weight, 3 kg) were subjected to CPB with a hydraulically driven physiologic pulsatile pump (PPP; n = 7), Jostra-HL 20 pulsatile roller pump (Jostra-PR; n = 6), Stockert SIII pulsatile roller pump (SIII-PR; n = 6), Stockert SIII mast-mounted pulsatile roller pump with a miniature roller head (Mast-PR; n = 7), Stockert SIII mast-mounted nonpulsatile roller pump (Mast-NP; n = 7), or Stockert CAPS nonpulsatile roller pump (CAPS-NP, n = 7). Once CPB was begun, each animal underwent 20 minutes of hypothermia, 60 minutes of DHCA, 10 minutes of cold reperfusion, and 40 minutes of rewarming. The pump flow rate was maintained at 150 ml·kg–1·min–1 and the mean arterial pressure (MAP) at 45 mm Hg. In the pulsatile experiments, the pump rate was kept at 150 bpm and the stroke volume at 1 ml/kg. The SHE (ergs/cm3) = 1,332 ([(∫ fpdt) / (∫ fdt)] – MAP) was calculated at each experimental stage. During normothermic CPB (15 minutes on pump), the physiologic pulsatile pump generated the highest surplus hemodynamic energy (8,563 ± 1,918 ergs/cm3, p < 0.001) compared with all other pumps. The Jostra HL-20 and Stockert SIII pulsatile roller pumps also produced adequate surplus hemodynamic energy. Nonpulsatile roller pumps and the Stockert SIII mast-mounted pulsatile roller pump did not generate any extra hemodynamic energy. During hypothermic CPB and after DHCA and rewarming, the results were extremely similar to those seen during normothermic CPB. The surplus hemodynamic energy formula is a novel method to precisely quantify different levels of pulsatility and nonpulsatility for direct and meaningful comparisons. The PPP produced the greatest surplus hemodynamic energy. Most of the pediatric pulsatile pumps (except Mast-PR) generated significant surplus hemodynamic energy. None of the nonpulsatile roller pumps generated adequate surplus hemodynamic energy.

Evaluation of the Mitral Valve Leaflet Morphology after Mitral Valve Reconstruction with a Concept “Coaptation Length Index”

Abstract  Background: In clinical settings, information on morphology of mitral valve leaflet after mitral valve reconstruction is limited. Methods: Between January 1996 and June 2000, 36 underwent mitral valve repair for mitral regurgitation (MR). The etiology of mitral insufficiency was prolapse, dilated annulus, and ischemic. Ring annuloplasty was performed in all cases. Mitral valve short‐axis dimension (MVd), vertical distance between annular line and closing point (Vd), coaptation length (CL), coaptation length index (CL/MVd) were measured by the two‐dimensional transesophageal echocardiography for the present 11 cases. Results: In 11 cases, residual MR, using a scale from 0 to 4, was 0 in 5 patients, 1 in 4 patients, 2 in 2 patients whose etiology of regurgitation was cardiomyopathy. MVd and Vd decreased significantly (38.7 ± 6.2 to 27.0 ± 5.6 mm, 10.1 ± 7.7 to 6.5 ± 4.6 mm, respectively). CL and CLI increased significantly (6.4 ± 2.4 to 11.6 ± 4.6 mm, 0.16 ± 0.06 to 0.44 ± 0.21, respectively). Among those index, only CLI have a statistically significant negative correlation with the degree of residual MR. Conclusion: The mitral valve ring annuloplasty produce the morphologic change of mitral apparatus, especially the increase of CLI, which may be one of the main factors in regulation of regurgitation.

Does Stringent Restrictive Annuloplasty for Functional Mitral Regurgitation Cause Functional Mitral Stenosis and Pulmonary Hypertension

Background— It remains controversial whether restrictive mitral annuloplasty (RMA) for functional mitral regurgitation (MR) can induce functional mitral stenosis (MS) that may cause postoperative residual pulmonary hypertension (PH). Methods and Results— One hundred eight patients with left ventricular (LV) dysfunction and severe MR underwent RMA with stringent downsizing of the mitral annulus. Systolic pulmonary artery pressure (PAP) and mitral valve performance variables were determined by Doppler echocardiography prospectively and 1 month after RMA. Fifty-eight patients underwent postoperative hemodynamic measurements. Postoperative echocardiography showed a mean pressure half-time of 92±14 ms, a transmitral mean gradient of 2.9±1.1 mm Hg, and a mitral valve effective orifice area of 2.4±0.4 cm2, consistent with functional MS. Doppler-derived systolic PAP was 32±8 mm Hg, which correlated weakly with the transmitral mean gradient (&rgr;=0.23, P=0.02). Postoperative cardiac catheterization also showed significant improvements in LV volume and systolic function, pulmonary capillary wedge pressure, cardiac index, and systolic PAP; the latter was associated with LV end-diastolic pressure [standardized partial regression coefficient (SPRC)=0.51], pulmonary vascular resistance (SPRC=0.47), cardiac index (SPRC=0.37), and transmitral pressure gradient (SPRC=0.20). In a multivariate Cox proportional hazard model, postoperative PH (systolic PAP >40 mm Hg), but not mitral valve performance variables, was strongly associated with adverse cardiac events. Conclusions— RMA for functional MR resulted in varying degrees of functional MS. However, our data were more consistent with the residual PH being caused by LV dysfunction and pulmonary vascular disease than by the functional MS. The residual PH, not functional MS, was the major predictor of post-RMA adverse cardiac events.

Advanced left-atrial fibrosis is associated with unsuccessful maze operation for valvular atrial fibrillation

OBJECTIVE Atrial dilatation and fibrosis are considered to be important factors in the occurrence and maintenance of atrial fibrillation (AF). However, the relationship between those structural remodeling and postoperative sinus conversions after a maze operation has been rarely studied. The purpose of this study was to determine whether pathological evaluation of atrial tissues was useful for predicting an unsuccessful maze operation in patients with valvular AF. METHODS Between March 2006 and June 2007, left-atrial tissues in the posterior wall and right-atrial appendage were obtained from 47 consecutive patients (24 patients with chronic AF, and 23 with sinus rhythm) undergoing mitral valve surgery (MVS). A concomitant maze operation was performed for all patients with chronic AF. Atrial cell diameters were measured using hematoxylin and eosin staining, and quantitative assessment of atrial fibrosis was performed with Masson trichrome staining using an image analyzer (Image Processor for Analytical Pathology, Sumika Technoservice Co., Hyogo, Japan). RESULTS Successful MVS was performed for all patients and there were no complications associated with tissue sampling. Patients with chronic AF had more advanced histological features in both atria as compared with those with sinus rhythm. Sixteen of 24 patients, who underwent a maze operation, had successfully restored sinus rhythm (successful maze group), while that in the remaining eight was not restored (unsuccessful maze group). Patients in the unsuccessful maze group had a larger left-atrial dimension and cardiothoracic ratio as compared with those in the successful group, whereas the duration of AF was not significantly different. Patients in the unsuccessful maze group also had greater hypertrophy of cardiomyocytes and more extensive intercellular fibrosis in the left atrium, while there were no differences for right-atrial pathological features between the groups. Multivariate logistic analysis confirmed that a larger amount of left-atrial fibrosis (>15%) was significantly associated with an unsuccessful maze operation. CONCLUSIONS The present results suggested that advanced fibrosis in the left atrium, but not in the right atrium, might be significantly associated with an unsuccessful maze operation in patients with valvular AF.