Yoshihisa Nakao

Insulin-like growth factor-I improves recovery of cardiac performance during reperfusion in isolated rat heart by a wortmannin-sensitive mechanism.

Insulin-like growth factor-I (IGF-I) has been shown to produce a short-term positive inotropic effect (PIE) in the myocardium under nonischemic conditions. IGF-I also conferred cytoprotection against ischemia and reperfusion injury in various organs. IGF-I may, therefore, facilitate the recovery of postischemic cardiac function. Isolated and crystalloid-perfused rat heart was subjected to 25 min of normothermic ischemia followed by 30 min of reperfusion. IGF-I produced PIE in a dose-dependent manner at concentrations ranging between 1 and 100 nM under nonischemic conditions. Although 1 nM isoproterenol produced much greater PIE and myocardial energy conversion efficiency (MECE) than did 65 nM IGF-I in this condition, the same concentration of IGF-I administered during reperfusion conferred better recovery of left ventricular function and MECE compared with isoproterenol. The improved cardiac performance by IGF-I was associated with lower release of creatine kinase (CK). Wortmannin (100 nM), a specific inhibitor of phosphatidylinositol kinase (PI-3 kinase), abrogated IGF-I-induced improvement of contractile function and inhibition of CK release in the postischemic heart. We conclude that IGF-I administered during reperfusion accelerates recovery of cardiac performance and mitigates myocardial injury through a wortmannin-sensitive mechanism.

Dual Involvement of Coenzyme Q10 in Redox Signaling and Inhibition of Death Signaling in the Rat Heart Mitochondria

Coenzyme Q10 (CoQ) has long been utilized as a cardioprotective agent in various heart diseases. One of the most important mechanisms by which CoQ exerts cardioprotection is aerobic ATP production as a mobile electron carrier in the mitochondrial electron transfer chain. The ability of CoQ to afford myocardial protection is also attributed to its antioxidant property. However, CoQ may also act as a pro-oxidant through the generation of reactive oxygen species. Although excess oxidative stress is known to induce death signaling via cytochrome c release from mitochondria, it is now apparent that a brief exposure to oxidative stress stimulates redox signaling for acquisition of tolerance to oxidative stress. Therefore, we have investigated dual involvement of CoQ in redox signaling generation through enhanced production of reactive oxygen species and death signaling inhibition through antioxidation. Mitochondria were isolated from the rat heart and incubated with CoQ (10 or 100 microM) or its vehicle HCO 60 for 1 h. H2O2 and cytochrome c release from respiring mitochondria were increased by antimycin A (2 microM), an inhibitor of complex III respiratory chain, or by high Ca2+ (10 microM). This enhanced release of H2O2 was associated with an increase in lipid peroxidation as measured with 4-hydroxy-2-nonenal-modified proteins and with large amplitude swelling of mitochondria. CoQ potentiated H2O2 release from antimycin A- or high Ca(2+)-treated mitochondria, but was capable of inhibiting lipid peroxidation and large amplitude swelling, and attenuated cytochrome c release from the mitochondria. In addition, CoQ increased ATP synthesis by mitochondria. These results suggest that CoQ plays dual roles in mitochondrial generation of intracellular signaling. CoQ acts as a pro-oxidant that participates in redox signaling. CoQ also acts as an antioxidant that inhibits permeability transition and cytochrome c release, and increases ATP synthesis, thereby attenuating death signaling toward apoptosis and necrosis.

Fate of fibrin sealant in pericardial space

BACKGROUND Although fibrin sealant (Beriplast, Aventis Behring, Marburg, Germany) has been widely used as a supplementary measure for hemostasis during cardiac surgery in Europe and is becoming popular in the United States, the pharmocokinetics of fibrin sealant applied in pericardial space has not been elucidated. METHODS A small incision was made on the epicardial surface of the left ventricle of a rat, and the incision was sutured. Total 0.2 ml of fibrin sealant containing iodine 125 (125I)-labeled fibrinogen, aprotinin, blood coagulation factor XIII and thrombin was applied to the area around the suture line. RESULTS Distributions of 125I-labeled fibrinogen in the heart on postoperative days 1, 3, 7, and 14 were 48.2% +/- 1.8%, 20.7% +/- 2.2%, 0.15% +/- 0.02%, and 0.01% +/- 0.02%, respectively. The radioactivity was negligible in the blood, liver, spleen, and kidney except for the thyroid in which the radioactivity increased to 7.9% +/- 0.7% and 4.3% +/- 0.4%, respectively, on postoperative days 7 and 14. Iodine 125-labeled fibrinogen concentrations of the heart and other organs showed a similar change in the time course of distribution. Dense and thick fibrin network, observed on postoperative day 1, had dissipated and was thinner with collagen formation by postoperative day 7. CONCLUSIONS Fibrin sealant applied to the pericardial cavity regresses rapidly and plays an important role in wound healing.

Effects Of The Na+/H+ Exchange Inhibitor Cariporide (HOE 642) On Cardiac Function And Cardiomyocyte Cell Death In Rat Ischaemic–Reperfused Heart

1. Na+/H+ exchange has been implicated in the mechanism of reperfusion injury. We examined the effects of the cardiac‐specific Na+/H+ exchange inhibitor cariporide (HOE 642) on postischaemic recovery of cardiac function and cardiomyocyte cell death (i.e. necrosis and apoptosis).

Multiple papillary fibroelastoma with quadricuspid aortic valve.

had chronic rheumatoid arthritis; 9 patients (30%) had other underlying risk factors, such as congenital or degenerative heart valve disease or coagulation problem; and 3 patients (10%) had no risk factors. The majority of their patients underwent surgery for valve dysfunction. When patients can tolerate cardiac surgery with cardiopulmonary bypass, indications for surgery are valve dysfunction, recurrent embolic events, and mobile vegetation. Removal of vegetation and repair of the valve seem to be feasible if the vegetation is small and localized. Prognosis after valve replacement or repair for nonbacterial thrombotic endocarditis is unknown but depends on the underlying cause. Even if the previous femoropopliteal bypass was performed with the working diagnosis of Burger disease, it is unlikely because there was no arterial disease in the other leg. Because of the large size of the vegetation plus the possible delay of time between ischemic events, the patient’s limb ischemia was thought to be arterial embolization caused by the vegetation. His noncoronary aortic leaflet was atrophic, which may be a factor in causing nonbacterial thrombotic endocarditis. Despite the patient’s young age and good general condition, he should be monitored carefully for possible occult malignant disease.

Repair of a recurrent pseudoaneurysm of the ascending aorta in an atomic bomb survivor with myelodysplastic syndrome.

Abstract  The occurrence of infective aortic pseudoaneurysms tends to be intractable and difficult to treat. We experienced a very rare case of a recurrent infective pseudoaneurysm in the ascending aorta that occurred after cardiac surgery in an atomic bomb survivor with myelodysplastic syndrome. The pseudoaneurysm was successfully repaired using a femoral artery autograft with an omentopexy and the patient recovered well without any recurrence.

Reliability and efficacy of a monitoring system for an implanted pulse generator

Abstract The Selection 900/900E is a physiological pacing device with a sophisticated monitoring system for detecting and analyzing atrial arrhythmias. We have investigated the reliability and efficacy of the Selection monitoring system. Twelve patients with episodes of atrial tachyarrhythmias were implanted the with Selection device (7 men, 5 women, aged 73 ± 6 years old). Ten patients had sick sinus syndrome and two patients had a high degree of atrioventricular (AV) block. All patients underwent 24-h external Holter monitoring after the operation (136 ± 41 days) to evaluate the accuracy of the data recorded by the internal monitoring system. There was no significant difference in counter data between the 24-h external Holter and the internal monitoring systems. Four patients recorded an episode of atrial fibrillation by both systems. In two patients, the 24-h external Holter monitoring system misread DDI pacing after mode switching as sinus rhythm or pacing failure. In another patient, the featured function of this pacing device for atrial tachyarrhythmia was recognized as a sensing failure by the 24-h external Holter monitoring system. The Selection 900/900E monitoring system is a reliable and informative way to evaluate the relevance of pacing therapy.

Freehand Cryopreserved Mitral Valve Allograft With Flexible Ring in the Pig

OBJECTIVE Cryopreserved valve allografts have proven satisfactory in aortic and pulmonary positions but not mitrally because of the difficulty in properly aligning the mitral valve allograft due to the complex subvalvular apparatus. To make the surgical procedure easier, we developed a freehand cryopreserved mitral valve allograft with a flexible ring. METHODS Whole cryopreserved mitral valve allografts with the papillary muscle, chordae, and leaflets from donor pigs were implanted mitrally in recipient pigs under cardiopulmonary bypass divided into 2 experimental groups; control allografts without the ring (n = 6) (CA group) and allografts with a flexible ring (n = 7) (RA group). Postimplantation hemodynamics and valvular function were evaluated by measuring arterial pressure, left ventricular end diastolic pressure, and left atrial pressure and by evaluating 2-dimensional echocardiography. Allografts were evaluated pathohistologically after cryopreservation and surgery by light microscopy. RESULTS Hemodynamics did not differ significantly between groups. Aortic cross-clamping and Cardiopulmonary bypass times were significantly shorter in the RA group than the CA group (p < 0.05). Pigs requiring optional procedures with sutured annuloplasty and valvuloplasty numbered more in the CA group than the RA group. Postoperative echocardiography showed satisfactory mitral valve opening in diastole and good leaflet coaptation in systole in both groups. Light microscopic examination of cryopreserved allografts after surgery showed almost normal structures. CONCLUSIONS Acute hemodynamic function and morphology of freehand cryopreserved valve allografts implanted mitrally in pigs proved acceptable. Adaptation of the flexible ring to allografts might be useful for technical benefit to facilitate accurate positioning of mitral subvalvular apparatus at implantation.