Koso Egi

Synthetic Salusins as Cardiac Depressors in Rat

Using bioinformatic analyses of full-length, enriched human cDNA libraries, we recently identified salusins, multifunctional related peptides ubiquitously expressed in major human tissues. Salusins cause transient and profound hypotension when injected intravenously to rats, the hypotensive effect of salusin-&bgr; being especially striking. However, the mechanisms of this hypotensive action remain elusive. To determine whether salusins modulate cardiac function in rats, we studied serial changes of systemic hemodynamics and functions of isolated perfused working and nonworking hearts before and after salusin administration. Intravenous salusin-&bgr; administration to intact anesthetized rats caused a temporary rapid, profound decrease in aortic blood flow concomitantly with hypotension and bradycardia without affecting systemic vascular resistance. Salusin-&bgr;–induced hypotension and bradycardia were completely blocked by pretreatment with atropine, a muscarinic receptor antagonist, but not by propranolol. In isolated perfused working rat hearts, salusin-&bgr; significantly decreased cardiac output, aortic flow, and stroke work. However, it did not affect coronary flow in isolated working and nonworking hearts. Our results indicate that salusins induce potent hypotension via negative inotropic and chronotropic actions. Salusin-&bgr; promotes its actions by facilitating vagal outflows to the heart, whereas the negative inotropism of salusin-&bgr; is also mediated via a direct myotropic effect.

Reduction of systemic and cardiac adhesion molecule expression after off-pump versus conventional coronary artery bypass grafting.

ABSTRACT Cardiopulmonary bypass (CPB) and operative trauma are associated with increased expression of pro‐ inflammatory mediators. We determined the relative contribution of CPB on activation of cytokines and adhesion molecules in patients undergoing coronary revascularization by comparing them with patients receiving off‐pump coronary artery bypass grafting (OPCAB). Twenty‐six patients were assigned to either the OPCAB procedure using a suction device and regular sternotomy (n = 13), or were treated conventionally using extracorporeal circulation, blood cardioplegia, and hypothermic arrest (29°C‐31°C; n = 13). Systemic levels of TNF‐&agr; and the soluble adhesion molecules P‐selectin and intracellular adhesion molecule 1 (ICAM‐1) were assayed. Immunohistochemistry was used to account for cardiac‐specific expression of adhesion molecules in interventricular endomyocardial sections. Both systemic and endomyocardial expres‐ sion of adhesion molecules were lower in the OPCAB group. Coronary revascularization with CPB resulted in a significant higher expression of TNF‐&agr;, which was associated with P‐selectin and ICAM‐1 expression. This was accompanied with higher catecholamine requirement in the CPB group in the early postoperative period. Despite comparable surgical trauma, the OPCAB procedure without the use of CPB and cardioplegic arrest significantly reduces systemic and cardiac adhesion molecule expression and catecholamine requirement. Since the clinical course in the early postoperative period was comparable, larger trials are required to select the appropria te patient who benefits most from one or the other treatment regime.

Significance of Serum Atrial and Brain Natriuretic Peptide Release After Coronary Artery Bypass Grafting

AbstractPurpose. The aim of this study was to examine whether serial changes in endogenous levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) were associated with clinical status after coronary artery bypass grafting (CABG). Methods. Serial blood samples were collected from 14 patients preoperatively, 2, 5 and 8 h after cardiopulmonary bypass, then up to 7 days postoperatively. Follow-up was done 2 years later. Results. We found a significant increase from the preoperative values in ANP and BNP concentrations on postoperative days 1 and 3 (P ≪ 0.001). The elevated BNP concentration correlated with the preoperative values (r2 = 0.824, P = 0.0005). Retrospectively, the BNP concentrations after surgery in the patients who suffered cardiac events within 2 years were significantly higher than those in the patients free of cardiac events (P = 0.0023). Conclusion. The BNP concentration after CABG was found to be corrected with interim clinical status after surgery. Thus, it may be necessary for patients with a high postoperative BNP concentration to be closely monitored for coronary events.

Perfusion flow assessment of coronary shunt during off-pump coronary artery bypass grafting.

BACKGROUND Coronary shunts are widely used to prevent myocardial ischemia during off-pump coronary artery bypass graft (OPCAB) procedures. Although clinical effectiveness has been reported, actual perfusion flow has not been well assessed. The purpose of this study was to evaluate actual shunt flow and its pattern during passive coronary perfusion in clinical OPCAB. METHODS In 15 OPCAB cases, the coronary perfusion flow of the external shunt (1.7 or 2.0 mm) during anastomosis and the free flow of the shunt were measured with an in-line electromagnetic or ultrasonic flow probe. The perfused coronary blood vessel was either the left anterior descending coronary artery or the right coronary artery. The inflow vessel of the external shunt was either the femoral artery (FA) or the ascending aorta (AA). RESULTS Free flow values of a 1.7-mm FA shunt, 1.7-mm AA shunt, and 2.0-mm FA shunt were 34+/- 7, 39 +/- 3, and 44 +/- 7 mL/min. Perfusion flows were 13 +/- 4, 14 +/- 3, and 22 +/- 4 mL/min, respectively. Perfusion flow was significantly lower than free flow and correlated well with coronary resistance. Although inflow site did not influence net perfusion flow, diastolic/systolic flow fraction ratio was significantly greater when the shunt was perfused from the FA. CONCLUSIONS External shunt from FA would provide limited but effective perfusion flow with a physiological pattern, which is passively regulated by coronary resistance.

Complete His-ventricular block, atrial flutter and ventricular tachycardia as arrhythmogenic activities in a patient with takotsubo cardiomyopathy

An association of atrial arrhythmias with takotsubo cardiomyopathy (TTC) has not been described previously. Here we report a 65-year-old male patient with TTC. The sudden appearance of atrioventricular block and subsequent bradycardia are believed to be key contributing factors for the development of TTC. Both ventricular tachyarrhythmia and various atrial arrhythmias, such as atrial flutter and atrial fibrillation, were observed during the initial management of the patients TTC. We speculate that both the left ventricular contractile dysfunction and the arrhythmogenic activities may share a common underlying etiology in advanced heart failure patients with TTC. <Learning objective: We describe a case of TTC complicated by ventricular tachycardia, atrial tachyarrhythmias, and an atrioventricular conduction disturbance and discuss the etiology of arrhythmogenic activities in TTC.>.