Mitsumasa Hata

Low-dose continuous infusion of human atrial natriuretic peptide during and after cardiac surgery

BACKGROUND We evaluated the effects of human atrial natriuretic peptide (hANP) during cardiopulmonary bypass (CPB). METHODS Forty patients undergoing coronary artery bypass grafting were investigated. A group of patients given hANP for 24 hours from the start of CPB (hANP group) was compared with a non-hANP group. Parameters examined were hemodynamics, urine volume, dosage of furosemide, respiratory index, pleural effusion, ANP, cyclic guanosine monophosphate, renin activity (renin), angiotensin-II, aldosterone, and glomerular filtration rate. RESULTS Central venous pressure, systemic vascular resistance index, and pulmonary vascular resistance index were significantly lower in the hANP group than in the non-hANP group. The hANP group showed significantly higher levels of ANP, cyclic guanosine monophosphate, glomerular filtration rate, and respiratory index, and significantly lower levels of renin, angiotensin-II, aldosterone, and pleural effusion, as compared with the non-hANP group. The dosage of furosemide was significantly lower and the urine volume was significantly larger in the hANP group. CONCLUSIONS hANP can satisfactorily compensate for the shortcomings of CPB by decreasing the peripheral vascular resistance, suppressing the renin-angiotensin-aldosterone system, and exerting a strong diuretic effect.

Influence of Continuous Infusion of Low-Dose Human Atrial Natriuretic Peptide on Renal Function During Cardiac Surgery A Randomized Controlled Study

OBJECTIVES The purpose of this study was to determine the effect of human atrial natriuretic peptide (hANP) in patients who underwent coronary artery bypass grafting (CABG) on renal function. BACKGROUND Acute renal failure after cardiac surgery is associated with high morbidity and mortality. METHODS A total of 504 patients who underwent CABG were divided into 2 groups: 1 group received hANP at 0.02 microg/kg/min from the start of cardiopulmonary bypass (hANP group), and 1 group did not receive hANP (placebo group). Various parameters were measured before and after surgery. RESULTS There was no difference in mortality between the 2 groups, but post-operative complications were less frequent in the hANP group (p = 0.0208). In the hANP group, serum creatinine (Cr) was significantly lower and urinary Cr and Cr clearance were significantly higher from post-operative day 1 to week 1. The maximum post-operative Cr level and percent increase of Cr were significantly lower in the hANP group (p < 0.0001). Patients with Cr exceeding 2.0 mg/dl included 1 in the hANP group and 8 in the placebo group, showing a significant difference (p = 0.0374). Four patients in the placebo group and none in the hANP group required hemodialysis, but the difference was not statistically significant. CONCLUSIONS Continuous infusion of low-dose hANP from the start of cardiopulmonary bypass effectively maintained post-operative renal function. Infusion of hANP prevents early post-operative acute renal failure and helps to achieve safer cardiac surgery. ( CLINICAL TRIAL REGISTRATION NUMBER UMIN000001440).

Results of low-dose human atrial natriuretic peptide infusion in nondialysis patients with chronic kidney disease undergoing coronary artery bypass grafting: the NU-HIT (Nihon University working group study of low-dose HANP Infusion Therapy during cardiac surgery) trial for CKD.

OBJECTIVES The purpose of this comparative study is to prove the efficacy of the human atrial natriuretic peptide (hANP) in patients with chronic kidney disease (CKD) undergoing coronary artery bypass graft surgery (CABG). BACKGROUND CKD is an important risk factor for cardiac surgery. METHODS This was a randomized controlled study of 303 patients with CKD who underwent CABG, and were divided into a group who received carperitide infusion and another group without carperitide. The primary endpoints were: 1) the post-operative dialysis-free rate; and 2) serum creatinine (sCr) and estimated glomerular filtration rate. The secondary endpoints were: 1) the early post-operative outcome; 2) outcome at 1 year post-operatively; 3) the maximum sCr, the rate of increase of sCr, and an increase of sCr by ≥ 0.3 mg/dl compared with the pre-operative value; and 4) ANP and cyclic-guanosine monophosphate levels. RESULTS The post-operative sCr was significantly lower in the hANP group not only in the post-operative acute stage but also in the first year. The maximum Cr and Cr increase rate were significantly lower in the hANP group (p = 0.00665, p < 0.0001). There was no difference in mortality rate in the first year post-operatively, and fewer cardiac events and patients going on dialysis were found in the hANP group (p < 0.0001 and p = 0.0014, respectively). CONCLUSIONS In the post-operative acute stage, carperitide showed cardiorenal protective effects that prevented post-operative cardiac events and initiation of dialysis. Thus, perioperative infusion of low-dose carperitide may have a significant role in management of patients with renal dysfunction undergoing on-pump CABG. (Effectiveness of hANP for Cardiac Surgery in Patients With Moderate to Severe Preoperative Renal Dysfunction Without Dialysis [NU-HIT for CRF]; UMIN000001462).

Optimal treatment of type B acute aortic dissection: long-term medical follow-up results.

BACKGROUND The aim of this study is to assess the long-term outcome of medical treatment and determine recent surgical indications for type B acute aortic dissection. METHODS In the last 8 years, 79 patients were admitted to our hospital with type B acute aortic dissection. We medically treated patients at the time of onset, regardless of the aortic diameter and blood patency status in the false lumen. If the maximum diameter of dissected aorta exceeded 60 mm in any stage, early or elective surgery was performed. The mean follow-up duration was 41.2 months. We evaluated operation free rate and actuarial survival rate. RESULTS Thirteen patients underwent early or elective operations of the descending aorta. At the time of onset, the maximum aortic diameter of these patients was significantly larger than that of medically managed patients (55.8 +/- 4.4 mm vs 44.6 +/- 8.2 mm; p = 0.0004). Two patients underwent emergency axillo-femoral bypass for leg ischemia. Of the other 64 patients, who were medically managed, 2 patients had type A dissection develop during follow-up, 3 died during the initial hospital stay (1 from rupture, 1 from bronchial asthma, and 1 from gut ischemia), and 1 died of pneumonia 6 months after onset. Operation free rate was 98.6% at 1 month, 90.0% at 1 year, 78.7% at 3 years, and 69.5% at 8 years. Actuarial survival rate of medically managed patients was 98.4% at 1 month and 93.5% at 8 years. CONCLUSIONS Medical treatment of type B acute aortic dissection produced good results. Surgical intervention for type B dissection should be done when the maximum aortic diameter exceeds 60 mm.

Continuous Low-Dose Infusion of Human Atrial Natriuretic Peptide in Patients With Left Ventricular Dysfunction Undergoing Coronary Artery Bypass Grafting: The NU-HIT (Nihon University working group study of low-dose Human ANP Infusion Therapy during cardiac surgery) for Left Ventricular Dysfunction

OBJECTIVES Continuous low-dose infusion of human atrial natriuretic peptide (hANP) in patients undergoing cardiac surgery on cardiopulmonary bypass (CPB) inhibits the renin-angiotensin-aldosterone system and compensates for the adverse effects of CPB. BACKGROUND We examined the influence of hANP infusion on cardiac and renal function in patients with left ventricular dysfunction undergoing coronary artery bypass grafting (CABG). METHODS The subjects were 133 patients who underwent CABG and had a pre-operative ejection fraction < or =35%. They were randomized to receive 0.02 microg/kg/min of hANP from the initiation of CPB (hANP group) or placebo (saline) infusion. RESULTS Early post-operative mortality did not show a significant difference between the 2 groups, but perioperative complications were significantly less frequent in the hANP group (p = 0.015). Long-term all-cause mortality showed no difference, but the cardiac death-free rate at 5 or 8 years post-operatively was 98.5% in the hANP group and 85.5% in the placebo group (p = 0.0285). Post-operative ejection fraction was significantly larger and the post-operative brain natriuretic peptide level was significantly lower in the hANP group. Serum creatinine was significantly lower in the hANP group than the placebo group at 1 month, 6 months, and 1 year post-operatively, whereas the estimated glomerular filtration rate was significantly higher in the hANP group at these times. CONCLUSIONS In patients with left ventricular dysfunction undergoing CABG, hANP showed renal- and cardio-protective effects and reduced post-operative complications. It also improved the long-term prognosis. We suggest that hANP should be considered as part of perioperative management of patients with cardiac dysfunction undergoing cardiac surgery. (NU-HIT trial for LVD; UMIN000001652).

Study of the factors related to atrial fibrillation after coronary artery bypass grafting: a search for a marker to predict the occurrence of atrial fibrillation before surgical intervention.

OBJECTIVE Atrial fibrillation after cardiac surgery is a frequent complication. In this study we studied various factors in addition to trying to identify a marker that would predict the potential for atrial fibrillation before surgical intervention to prevent its occurrence. METHODS We targeted 234 cases in which isolated coronary artery bypass grafting had been performed. The items for study included age, EuroSCORE, and maximum values of creatine phosphokinase-MB, troponin I, and angiotensin II after surgical intervention and preoperative values of atrial natriuretic peptide, brain natriuretic peptide, and C-reactive protein. As fibrotic markers, we measured levels of the sialylated carbohydrate antigen KL-6 in the blood, hyaluronic acid, and pyridinoline cross-linked carboxyterminal telepeptide of type I collagen C. At the time of surgical intervention, a section of the right atrium was extracted, and atrial natriuretic peptide, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels were measured. RESULTS Atrial fibrillation was observed in 73 (31.2%) cases, and preoperative factors that showed statistically significant differences in the occurrence of atrial fibrillation included age, EuroSCORE, and preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood. As for intraoperative and postoperative factors, statistically significant differences were observed in the postoperative maximum of angiotensin II, atrial natriuretic peptide of the right atrium, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen levels. CONCLUSION The fibrosis of tissue associated with age is believed to be closely related to the occurrence of atrial fibrillation after coronary artery bypass grafting. This study suggests that the preoperative values of atrial natriuretic peptide, angiotensin II, the sialylated carbohydrate antigen KL-6, hyaluronic acid, and pyridinoline cross-linked telopeptide of type I collagen in the blood are useful as a new index for the occurrence of atrial fibrillation after coronary artery bypass grafting.

Should emergency surgical intervention be performed for an octogenarian with type A acute aortic dissection

OBJECTIVE The number of octogenarians undergoing emergency surgery is increasing and may negate the impact of the beneficial advances. The aim of this study was to review octogenarians with type A acute aortic dissection and assess the prognosis. METHODS Fifty-eight patients with acute aortic dissection, whose average age was 83.2 years, were divided into 2 groups: Group I comprised 30 patients who underwent emergency surgery, and group II comprised 28 patients who were treated conservatively. We compared the 2 groups in terms of mortality and morbidity. RESULTS In group I, postoperative hospital mortality was 13.3% (4 patients). In group II, 17 patients (60.7%) died in the hospital. In group I, although emergency aortic replacement was successfully completed, 5 patients became bedridden after surgery and 2 patients died of pneumonia or stroke in the early stages of institutional care. Thirteen patients in group I died of malignancies, abdominal aortic rupture, traffic accident, heart failure, or late-stage senility in later phase. There was no difference in actuarial survivals at 5 years, which were 48.5% in group I and 35.4% in group II. CONCLUSION Emergency surgery for octogenarians with acute aortic dissection showed acceptable mortality. However, families had to take responsibility for patients who experienced unconsciousness, had dementia, or became bedridden. It is important to have consensus between the family and surgeons about emergency surgical treatment for octogenarians.

The Role of Pulsatility in End-Organ Microcirculation After Cardiogenic Shock

To estimate the effectiveness of pulsatility in end-organ microcirculation after cardiogenic shock, experimental studies using swine were done. Cardiogenic shock was produced in 14 pigs by ligating the left anterior descending branches so that mean aortic pressure dropped to 60% of the control value. After inducing shock, left atrial to ascending Ao bypass was initiated. A pneumatic pulsatile pump (Zeon Medical Inc, Tokyo, Japan) was used in seven pigs (Group P) and a centrifugal pump (BP-80, BioMedicus Inc, Minneapolis, MN) in seven (Group NP). In both groups, about half the usual cardiac output was supported for 3 hr, maintaining mean aortic pressure at approximately 100 mm Hg. The pulse pressure was 36.6 +/- 4.6 mm Hg in Group P, and 14.3 +/- 1.5 mm Hg in Group NP. Epicardial and endocardial regional flows recovered after assist in both groups. There were no significant differences between the two groups. However, liver tissue flow, renal cortex flow, and stomach mucous flow in Group P was significantly higher than those of Group NP after support (p < 0.05). In addition, arterial blood ketone ratio in Group P was 0.61 +/- 0.13 vs 0.39 +/- 0.06 in Group NP, a significant difference (p < 0.05). These results suggest that in uneven blood flow distribution of end organs after cardiogenic shock, pulsatility was effective in improving and maintaining function and microcirculation of end organs, preventing multiorgan failure.

Feasibility of landiolol and bisoprolol for prevention of atrial fibrillation after coronary artery bypass grafting: A pilot study

BACKGROUND We previously performed a trial of intravenous landiolol hydrochloride during and after cardiac surgery (the PASCAL trial) and demonstrated a preventive effect on postoperative atrial fibrillation (AF). In the present study, we investigated the efficacy of increasing the dose and administration period of landiolol for prevention of postoperative AF, as well as the effect of oral bisoprolol in the early postoperative period. PATIENTS AND METHODS A total of 105 patients who underwent coronary artery bypass grafting were randomized to 3 groups: a group receiving intravenous landiolol perioperatively at 5 μg/kg/min for 3 days (group L), a group receiving oral bisoprolol postoperatively together with landiolol (group LB), and a control group without beta-blocker therapy (group C). The primary end point was the presence/absence of postoperative AF. Secondary end points were (1) the early clinical outcome, (2) hemodynamics, (3) cardiac enzymes (creatine kinase isoenzyme MB, troponin-I, and human heart fatty acid-binding protein), (4) high-sensitivity C-reactive protein (hs-CRP) and pentraxin-3, (5) asymmetric dimethylarginine (ADMA), and (6) brain natriuretic peptide. RESULTS Postoperative AF occurred in 14.5% of group L, 9.1% of group LB, and 35.3% of group C. A significant difference was observed between groups LB and C. Significantly higher levels of troponin-I, human heart fatty acid-binding protein, hs-CRP, pentraxin-3, and ADMA were noted in group C than in groups L and LB. CONCLUSIONS Landiolol and bisoprolol prevented postoperative AF. The anti-ischemic, anti-inflammatory, and anti-oxidant effects of these beta-blockers presumably inhibited the onset of AF.

Efficacy of Aggressive Lipid Controlling Therapy for Preventing Saphenous Vein Graft Disease

BACKGROUND We assessed the efficacy of aggressive lipid controlling therapy (ALCT), which maintains low-density lipoprotein cholesterol (LDL-C) below to 80 mg/dL and LDL/high-density lipoprotein cholesterol (HDL-C) ratio less than 1.5 for preventing postcoronary bypass (CABG) saphenous vein graft (SVG) diseases by using intracoronary angioscopy. METHODS Twenty-one patients after CABG were divided into two groups: group I consisted of 10 patients whose serum LDL-C level and LDL/HDL could be controlled less than 80 mg/dL and 1.5, respectively, by rosuvastatin for about one year; group II consisted of 11 patients whose LDL-C level and LDL/HDL have been higher than 100 mg/dL and 2.5, respectively, regardless of having medication of pravastatin. Twenty-seven SVGs were assessed by intravascular ultrasound (IVUS) and angioscopy on postoperative 12 to 16 months. RESULTS The serum LDL-C level (I: 64.1 vs II: 130.2 mg/dL) and LDL/HDL (I: 1.36 vs II: 2.64), and high sensitive C-reactive protein (I: 0.045 +/- 0.100 vs II: 0.116 +/- 0.020 mg/dL) were significantly lower in group I. In group II, IVUS detected eccentric plaques in 11 (78.6%) of 14 SVGs. Furthermore the angioscope showed yellow plaque in all 14 SVGs (100%) and 11 (78.6%) of them had thrombi. On the other hand, in group I, all 13 SVGs had no eccentric, yellow plaques or thrombi and the intima was entirely clear white. CONCLUSIONS Prophylactic treatment for yellow plaque and thrombus formation are extremely important in the development of early and late SVG disease. Aggressive lipid controlling therapy is quite attractive to avoid post CABG SVG disease and may be effective to maintain the long-term graft patency.