Nobuo Sakagoshi

Effect of a cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, on myocardial reperfusion injury

A new cyclic adenosine monophosphate phosphodiesterase inhibitor, DN-9693, was examined to see whether myocardial reperfusion injury could be reduced in a setting of cardioplegic arrest through its antiaggregation effect on leukocytes. Isolated rabbit heart models with whole blood perfusion were used, and 18 hearts were divided into three groups according to the reperfusion method: control (G-1, n = 5), DN-9693 (G-2, n = 7), and leukocyte depletion (G-3, n = 6). The hearts were subjected to 120 minutes of cold global ischemia under crystalloid cardioplegia followed by 30 minutes of reperfusion. A dose of 20 micrograms.kg-1.min-1 of DN-9693 was administered in G-2, and a leukocyte removal filter was used in G-3 during reperfusion. Ultrastructural changes in mitochondrial injuries, intracellular edema, and capillary injuries of the myocardium showed worse changes in G-1 than in G-2 and G-3. Under microscopic study, the intracapillary leukocyte count was significantly higher in G-1 than in G-2 and G-3. Recovery of rate-pressure product, left ventricular developed pressure, and coronary flow were significantly better in G-2 and G-3 than in G-1. There were no significant differences between G-2 and G-3 for all these indices. These results indicate that reperfusion with leukocyte-depleted blood attenuates reperfusion myocardial injury and DN-9693 has a comparable myocardial protective effect with possible inhibition of leukocyte aggregation.

Relation between myocardial beta-adrenergic receptor and left ventricular function in patients with left ventricular volume overload due to chronic mitral regurgitation with or without aortic regurgitation

The relation between myocardial beta-adrenergic receptor and left ventricular (LV) function was studied in 10 patients, aged 41 to 61 years (average 51), with LV volume overload mainly due to chronic mitral regurgitation. Beta-adrenergic receptors were examined using crude membrane in LV papillary muscle obtained at mitral valve replacement. Cardiac function was evaluated at preoperative cardiac catheterization with the interval to surgery of 1 to 33 months (average 7). Beta-adrenergic receptor density in 7 patients with New York Heart Association class II or III congestive heart failure was higher than that in 3 patients with class IV heart failure (59 +/- 19 vs 37 +/- 3 fmol/mg protein, p less than 0.05). Beta-adrenergic receptor density showed a positive correlation with end-systolic stress/end-systolic volume index ratio, the index for contractile function (p less than 0.005). Other parameters such as cardiac index, pulmonary artery wedge pressure and LV ejection fraction had no significant correlation to beta-adrenergic receptor. The results demonstrated that increases in symptom and LV dysfunction, particularly of the contractile state, was associated with decreased myocardial beta-adrenergic receptor density from possible down-regulation in patients with chronic mitral regurgitation with or without aortic regurgitation.

Fulminant apical ballooning syndrome after replacement of a prosthetic aortic valve

A 70-year-old woman was readmitted to our hospital with a fever of 39°C on the 30th day after replacement of a prosthetic aortic valve. She required percutaneous cardiopulmonary support for her heart failure and was weaned after 7 days. Echocardiography revealed an akinetic and aneurysmally dilated left ventricular apex and hyperdynamic basal segments. This case indicates that fulminant apical ballooning syndrome might be added to the list of potential complications after cardiac surgery.

Effects of lithium ion on the inhibitory GTP-binding protein and its coupling response

Addition of lithium ion to the inhibitory GTP-binding (Gi) protein resulted in a decrease of its ADP-ribosylation by islet-activating protein (pertussis toxin, IAP). The possibility that this decrease was due to dissociation of the Gi protein trimer was examined. Results showed that lithium ions had no appreciable effect on either the Gi protein trimer or its dissociation into its three subunits induced by Mg2+ and GTP gamma S. Next, the effect of lithium ions on Gi protein-mediated adenylate cyclase inhibition and alpha 2-adrenoceptor in human platelet membranes was examined. Lithium ion was found to impair adenylate cyclase inhibition of alpha 2-adrenoceptor stimulation of forskolin-stimulated enzyme activities. The monovalent ion also abolished guanine nucleotide modulation (GTP shift) of agonist binding, while it had no remarkable effects on antagonist binding in alpha 2-adrenoceptor of human platelet membranes. These results suggested that lithium ion caused functional change of the Gi protein without remarkable change of its dissociation, causing modulation in a coupling between alpha 2-adrenoceptor and Gi protein.

A technique to protect an axillo-coronary bypass graft

We describe a simple technique to protect an axillo-coronary bypass graft with a stretch, thin-walled 6-mm polytetrafluoroethylene graft with removable rings.

Enhancement of β-adrenoceptor function after reperfusion following cardioplegic arrest in rat hearts

We investigated alterations in a beta-adrenoceptor (BAR) system after reperfusion following hypothermic ischemia induced by a high-potassium (18 meq/liter) cardioplegic solution in isolated rat hearts. Materials were divided into two groups: the reperfusion group (Gr-R, n = 5) with 40 min reperfusion following 40 min cardioplegic arrest (10 degrees C) and the control group (Gr-C, n = 5) with no ischemia as time-matched perfused control. BAR and adenylate cyclase activities in crude membrane fractions were compared. Results showed that basal, NaF-, and forskolin-stimulated adenylate cyclase activity did not differ between the two groups. The maximal enzyme activity in the presence of 10(-4) M (-)-isoproterenol was higher in Gr-R than in Gr-C, while the net activity stimulated by (-)-isoproterenol was 74% higher in Gr-R than in Gr-C. The [125I]Iodocyanopindolol [( 125I]CYP) binding assay showed that BAR density was 14% higher in Gr-R than in Gr-C, while the affinity was not significantly different. The IC50 values of (-)-isoproterenol for [125I]CYP binding were lower in Gr-R than in Gr-C and the proportion of high-affinity binding sites was higher in Gr-R than in Gr-C. These data showed that 40 min reperfusion following hypothermic cardioplegic arrest (40 min) resulted in significant increases in myocardial BAR density and maximal (-)-isoproterenol-stimulated adenylate cyclase activity, and enhancement of BAR affinity for beta-adrenergic agonists due to the increase in the proportion of high-affinity binding sites.

Mitral valve repair, tricuspid valve annuloplasty, and ligation of coronary artery-pulmonary trunk fistula in a patient with arrhythmogenic right ventricular cardiomyopathy.

Abstract  Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a rare cardiac disorder characterized by replacement of myocytes with adipose and fibrous tissue and often presents with ventricular arrhythmia, heart failure, and sudden death. This report describes a 67‐year‐old man with ARVC complicated with severe mitral regurgitation, dilated annulus of the tricuspid valve, and coronary artery‐pulmonary artery fistula. Mitral valve repair, tricuspid valve annuloplasty, and ligation of the coronary artery‐pulmonary artery fistula were performed. The postoperative course was uneventful, and the patient was discharged on postoperative day 15. (J Card Surg 2011;26:274‐276)

Alterations in the beta-adrenergic receptor system after hypothermic ischemia in hearts with preischemic beta-receptor desensitization

Although hypothermic cardioplegic arrest is a basic method of myocardial protection in cardiac surgery, the beta-adrenergic receptor (BAR) system has been little investigated in the heart subjected to hypothermic ischemia. Additionally, although the hypothermic arrest is often induced in hearts with preischemic desensitization of the BAR system by preceding congestive heart failure, the functional state of the BAR system after ischemia has not been studied in these hearts. We investigated alterations in the BAR system after hypothermic ischemia in normal rat hearts and in those with preischemic desensitization of the BAR system produced with isoproterenol (ISP: 400 micrograms/kg/hr for 24 hr). Both normal and BAR-desensitized hearts were isolated and subjected either to 40 min of hypothermic (10 degrees C) global ischemia followed by 40 min of reperfusion or subjected to time-matched aerobic perfusion with modified Krebs-Henseleit solution. At the end of perfusion (1) BAR binding properties with [3H]CGP-12177 and adenylate cyclase activity were measured in crude membrane fraction and (2) the inotropic response to ISP (delta LV + dP/dtmax) was evaluated in an isovolumetric contracting heart preparation. Following reperfusion, normal hearts without desensitized BAR showed a higher Bmax value than those of nonischemic time-matched hearts (41.8 +/- 3.1 vs 35.4 +/- 2.4 fmole/mg protein, P less than 0.05), whereas the Kd value was in a similar range in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Right atrial approach for repairing a posterior ventricular septal rupture: a case report.

BackgroundVentricular septal rupture (VSR) is a life-threatening complication following acute transmural myocardial infarction. Posteriorly located ruptures are one of the main predictors of poor prognoses because of the surgical difficulties associated with this location.Case presentationA 72-year-old man with a posterior VSR underwent surgical repair via the right atrial approach. The patient’s postoperative course was uneventful, and echocardiography showed no residual shunt flow. He was discharged on postoperative day 37.ConclusionBy temporally detaching the tricuspid valve leaflet, this approach provides a better view and handling space within the posterior ventricular septum than the trans-ventricular approach. Additionally, avoiding a ventricular incision can better preserve postoperative ventricular function.

A Case Report of Type A Dissecting Aneurysm Occurring after Aortic Valve Replacement

症例は4年前に大動脈弁置換術を施行された67歳,男性.胸部CTで胸骨裏面に接する直径10cmの偽腔開存型解離性上行大動脈瘤を認めたため手術となった.胸骨再正中切開や瘤周囲剥離中の大出血とこれに関連した脳血流確保が問題であった.両側総頸動脈を頸部で露出して脳分離体外循環に備え,大腿動静脈からの部分体外循環下に胸骨再正中切開・縦隔内剥離を行った.胸骨再正中切開は問題なかったが,大動脈弓部や上行大動脈頭側が高度癒着のためにまったく剥離できなかった.血液温を23℃に冷却し,両側総頸動脈からの脳分離体外循環下に大動脈基部を切開した.解離のentryは大動脈弁置換術時の大動脈切開部右半分で,これをePTFEパッチで閉鎖した.MRSA肺炎などのため長期入院となったが,術後14ヵ月目の現在,元気に通院している.