Nobuo Tsunooka

Capillary Leakage in Cardiac Surgery with Cardiopulmonary Bypass

Cardiopulmonary bypass causes a systemic inflammatory response, which can lead to capillary leak syndrome. In 15 adults undergoing elective cardiac surgery with cardiopulmonary bypass, we determined the volume and peak time of capillary leakage from the measurements of extracellular fluid volume and circulating blood volume taken preoperatively, at various intervals up to 24 hours after surgery, and on the 7th postoperative day. Extracellular fluid volume rose from 15.5 ± 2.7 Lpreoperatively to a peak 4 hours after surgery of 18.3 ± 3.2 L and remained elevated at 24 hours. Circulating blood volume fell from 4.10 ± 0.68 L preoperatively to 3.20 ± 0.58 L at the end of surgery. Fluid administered intraoperatively did not raise the circulating blood volume. Intraoperative fluid balance was positive at 2.62 ± 0.72 L but negative at all time points postoperatively. There was significant postoperative capillary leakage, increasing from 4.7% ± 2.3% of body weight at the end of surgery to a peak 4 hours later of 5.4% ± 2.0% and falling to 2.8% ± 3.3% at 24 hours. This knowledge of the pattern of change in capillary leakage after cardiac surgery with cardiopulmonary bypass might serve as a valuable guide for postoperative management.

Intestinal ischemia/reperfusion-induced bacterial translocation and lung injury in atherosclerotic rats with hypoadiponectinemia.

BACKGROUND Intestinal ischemia/reperfusion causes intestinal mucosal injury, which may result in bacterial translocation (BT) and multiple organ failure. Lung injury is a common complication after intestinal ischemia/reperfusion. Adiponectin is an antiinflammatory adipokine, and it plays an important role in the development of metabolic syndrome in hypoadiponectinemia. In atherosclerosis with hypoadiponectinemia, BT also may aggravate injuries induced by intestinal ischemia/reperfusion. METHODS Wistar rats were divided into 3 groups: Normal group (normal diet), Chol group (2% high cholesterol diet), and Chol+1400W group (Chol group plus 1400W, an inducible nitric oxide [iNOS] inhibitor, at 1 mg/kg intraperitoneally 30 minutes preoperatively). The serum concentrations of lipids and adiponectin and vascular responses were measured. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 minutes, followed by 360 minutes of reperfusion (T1). Intestinal injury was assessed from microcirculatory flow, histology, serum diamine oxidase activity, and permeability. Lung injury was assessed by histology, pulmonary permeability index (PPI), and wet-to-dry lung weight (W/D) ratio. Intestinal and lung nitric oxide (NO) concentrations were also measured. BT was assessed by serum peptidoglycan (PG) concentration. RESULTS The Chol and Chol+1400W groups developed hyperlipidemia and hypoadiponectinemia; the 2 groups also had vascular endothelial dysfunction without histological changes, indicating early atherosclerosis. These groups also showed poor recovery of intestinal microcirculatory flow at T1. The serum diamine oxidase activity, histological intestinal damage, and permeability were elevated at T1 in the Chol group; however, these findings were not significant in the Normal and Chol+1400W groups. Histological lung damage and lung PPI and W/D ratio were increased only in the Chol group. Intestinal and lung NO concentrations were significantly elevated at T1 in the Chol group. The serum PG concentration was elevated significantly in the Chol group. CONCLUSION In atherosclerotic rats with hypoadiponectinemia, intestinal microcirculatory flow does not recover adequately after intestinal ischemia/reperfusion because of endothelial dysfunction. Atherosclerosis with hypoadiponectinemia increased the incidence of BT further by aggravating intestinal mucosal injury and, moreover, it aggravated lung injury. Although inhibition of iNOS does not lead to adequate recovery of intestinal microcirculatory flow, it reduces injury by decreasing the amount of NO derived from high enzymatic iNOS activity in the intestine.

Pitavastatin prevents intestinal ischemia/reperfusion-induced bacterial translocation and lung injury in atherosclerotic rats with hypoadiponectinemia

BACKGROUND Atherosclerosis with hypoadiponectinemia can be further aggravated by intestinal ischemia/reperfusion (II/R)-induced injuries, such as bacterial translocation and lung injury. We investigated the effect of statin administration on the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia. METHODS Wistar rats were divided into 4 groups: (1) the Normal group (normal diet), (2) the Chol group (2% high cholesterol diet), (3) the St-1w group, and (4) the St-2w group (Chol group plus pitavastatin administration for 1 or 2 weeks, respectively). The serum concentrations of lipids and adiponectin were measured preoperatively. After midline laparotomy (time, T0), the superior mesenteric artery was occluded with a microvascular clamp for 30 min, followed by 360 min of reperfusion (T1). Intestinal and lung nitric oxide (NO) concentrations were measured. Intestinal injury was assessed by microcirculatory flow, histology, and permeability. Bacterial translocation was assessed by analysis of serum peptidoglycan concentration. Lung injury was assessed by histologic examination, pulmonary permeability index, and wet/dry lung weight ratio. RESULTS The 2-week administration of statins with high-cholesterol feeding (St-2w group) improved hypoadiponectinemia to levels similar to those of the Normal group. Intestinal and lung NO concentrations were significantly lower at T1 in the Normal and St-2w groups than in the Chol group. Statin administration improved poor recovery of intestinal microcirculatory flow in the Chol group. At T1, intestinal and lung injuries were significantly aggravated and serum peptidoglycan concentration was significantly elevated in the Chol group compared with the Normal and St-2w groups. The 1-week administration of statins had no significant influence on serum adiponectin levels, tissue NO concentration, or tissue injury. CONCLUSION Administration of pitavastatin reduces the risk of II/R-induced injury in atherosclerotic rats with hypoadiponectinemia by improving hypoadiponectinemia and inhibiting inducible NO synthase-produced NO. Furthermore, preoperative improvement of hypoadiponectinemia may be important as an index of the protective effect of pitavastatin for II/R-induced injury in atherosclerotic rats with hypoadiponectinemia.

Ischemia of the intestinal mucosa during cardiopulmonary bypass.

Abstract Bacterial translocation is believed to occur during cardiopulmonary bypass (CPB) because serum endotoxin concentrations rise. Intestinal ischemia during CPB, however, has never been proven directly. The condition of the intestinal mucosa during CPB was studied by measuring serum diamine oxidase (DAO) activity, an index of intestinal ischemia. Serum DAO activity, blood lactate concentration, and the arterial ketone body ratio (AKBR) were measured intraoperatively in four successive patients who underwent aortic arch replacement by the open distal anastomosis method. DAO activity rose after restoration of blood flow to the lower half of the body, and continued to rise throughout CPB. The lactate concentration also rose, mirroring the change in DAO activity, and returned to nearly normal 12 h after the operation. The AKBR decreased during CPB, with a mean minimum vale of 0.16 ± 0.07 immediately after the restoration of blood flow to the lower half of the body. The parallel rise in DAO activity and serum lactate concentration once blood flow to the lower half of the body was restored implies that ischemic injury to the mucosa of the small intestine occurs during CPB. The continued rise in these parameters throughout CPB is consistent with ongoing injury due to splanchnic hypoperfusion, as reflected in the decrease in the AKBR during the same period.

Effects of a phosphodiesterase III inhibitor on circulating blood volume after cardiopulmonary bypass

Abstract Using a new method based on pulse dye densitometry, circulating blood volume (BV) was measured without direct sampling in patients undergoing open-heart surgery, and the effects of phosphodiesterase (PDE) III inhibitor administration during cardiopulmonary bypass (CPB) were evaluated. Sixteen patients scheduled for elective coronary artery bypass grafting were randomly assigned to the PDE III inhibitor group or control group. BV was determined before CPB, and immediately, and 4 and 12 h after operation. After declamping of the aorta, the PDE III inhibitor amrinone (1 mg/kg) was infused as a single bolus into the venous reservoir in the PDE III inhibitor group. BV decreased significantly soon after the operation in the control group. It did not decrease in the PDE III inhibitor group (48.6 ± 44 and 60.6 ± 8.0 ml/kg for the control and PDE III inhibitor groups, respectively). Four hours after surgery and beyond no significant changes in BV were observed in either group. The body fluid balance was negative in both groups. In conclusion, a single administration of PDE III inhibitor during CPB was found to sustain BV soon after operation and, therefore, is useful for postoperative management of open-heart surgery.

Pitavastatin Prevents Bacterial Translocation after Nonpulsatile/Low-Pressure Blood Flow in Early Atherosclerotic Rat: Inhibition of Small Intestine Inducible Nitric Oxide Synthase

Background: Cardiopulmonary bypass decreases intestinal mucosal blood flow because of nonpulsatile and low-pressure blood flow resulting in bacterial translocation (BT) and atherosclerosis also has peripheral blood flow deficiency. The risk of nonpulsatile and low-pressure blood flow for atherosclerotic animals and the effect of statin administration, which has pleiotropic effects, were studied. Methods: Wistar rats were divided into four groups: group N (normal diet), group C (high-cholesterol diet), group S (group C plus pitavastatin therapy), and group I [group C plus inducible nitric oxide (iNOS) inhibitor therapy]. First of all, vascular responses were measured. Then the rats underwent nonpulsatile/low-pressure blood flow in the intestine, and the serum peptidoglycan concentration as a parameter of BT, the small intestinal PO2 ratio (intestinal PO2/PaO2) as a parameter of mucosal blood flow, and NO concentrations were measured before surgery (T0), at the end of 90 min of stenosis (T1), and 90 min after the release of stenosis (T2). Immunostaining for nitrotyrosine was also performed at T2. Results: Group C had vascular endothelial dysfunction without histological changes, which indicated early atherosclerosis. The serum peptidoglycan concentration increased significantly at T2 only in group C. The intestinal PO2 ratio was decreased at T1 in all the groups, and retuned to baseline at T2 in group N and group S, but not in group C or group I. Jejunal NO only in group C was significantly higher at all time points and ileal NO production at T1 and T2. There tended to be a positive stain for nitrotyrosine along the mucosal epithelium in group C. Conclusion: In the setting of early atherosclerosis, intestinal blood flow does not only improve after nonpulsatile/low-pressure blood flow but causes BT because of a large amount of NO from high enzymatic intestinal iNOS activity, and pitavastatin treatment can prevent BT by improving both issues.

Cardiac surgery in patients with end-stage renal disease. Utility of continuous ambulatory peritoneal dialysis.

OBJECTIVES The number of patients with end-stage renal disease undergoing open heart surgery continues to grow. We evaluated continuous ambulatory peritoneal dialysis and the extracorporeal ultrafiltration method during cardiopulmonary bypass in the management of these difficult patients. METHODS These 2 methods were used in 4 patients with renal failure who underwent open heart surgery between July 1997 and March 1999. Preoperative continuous ambulatory peritoneal dialysis was conducted using standard protocols. Extracorporeal ultrafiltration method was used only during cardiopulmonary bypass. Continuous ambulatory peritoneal dialysis was initiated upon arrival at the intensive care unit. Mean follow-up was 12 months. RESULTS Postoperative blood urea nitrogen and creatinine concentrations were lower than preoperative concentrations. No patients required hemodialysis. All 4 patients were discharged to their homes. No deaths occurred. CONCLUSIONS Continuous ambulatory peritoneal dialysis and extracorporeal ultrafiltration method are combined to treat patients with end-stage renal disease who require open heart surgery. This combination is simple, and does not require specialized personnel, and obviates the hemodynamic instability associated with hemodialysis.

Perioperative Circulating Blood Volume and Cardiac Function in Valve Disease

Circulating blood volume is important in managing fluid balance and cardiac function after surgery under cardiopulmonary bypass. Appropriate management differs among the valve disorders, but perioperative blood volume has not yet been considered. From February 2001 to March 2003, perioperative blood volume, fluid balance, cardiac index, and left ventricular stroke work index were measured in 31 patients: 10 with aortic stenosis, 9 with aortic regurgitation, 3 with mitral stenosis, and 9 with mitral regurgitation. All immediate postoperative blood volume measurements were less than preoperative values, and gradually returned to baseline. At all time points, blood volume in patients with aortic or mitral regurgitation was high, whereas it was low in those with stenosis, especially mitral stenosis. Fluid balance was positive in all patients. Postoperatively, there was a positive correlation between cardiac index and blood volume in all groups. The left ventricular stroke work index in the mitral regurgitation group was significantly higher than other groups, the aortic stenosis group was slightly lower, the mitral stenosis and mitral regurgitation groups were higher than the baseline, and the aortic regurgitation group was essentially unchanged. Thus, it is necessary to consider blood volume perioperatively in different valvular diseases to manage water balance.