Biomedical subjects

Y Nakao

Publications and source records attributed to Y Nakao.

At least 37 records · Page 2Linked to original sources

PubMed2001

Protein kinase C isoform-dependent myocardial protection by ischemic preconditioning and potassium cardioplegia.

OBJECTIVE: Ischemic preconditioning combined with potassium cardioplegia does not always confer additive myocardial protection. This study tested the hypothesis that the efficacy of ischemic preconditioning under potassium cardioplegia is dependent on protein kinase C isoform. METHODS: Isolated and crystalloid-perfused rat hearts underwent 5 cycles of 1 minute of ischemia and 5 minutes of reperfusion (low-grade ischemic preconditioning) or 3 cycles of 5 minutes of ischemia and 5 minutes of reperfusion (high-grade ischemic preconditioning) or time-matched continuous perfusion. These hearts received a further 5 minutes of infusion of normal buffer or oxygenated potassium cardioplegic solution. The isoform nonselective protein kinase C inhibitor chelerythrine (5 micromol/L) was administered throughout the preischemic period. All hearts underwent 35 minutes of normothermic global ischemia followed by 30 minutes of reperfusion. Isovolumic left ventricular function and creatine kinase release were measured as the end points of myocardial protection. Distribution of protein kinase C alpha, delta, and epsilon in the cytosol and the membrane fractions were analyzed by Western blotting and quantified by a densitometric assay. RESULTS: Low-grade ischemic preconditioning was almost as beneficial as potassium cardioplegia in improving functional recovery; left ventricular developed pressure 30 minutes after reperfusion was 70 +/- 15 mm Hg (P <.01) in low-grade ischemic preconditioning and 77 +/- 14 mm Hg (P <.001) in potassium cardioplegia compared with values found in unprotected control hearts (39 +/- 12 mm Hg). Creatine kinase release during reperfusion was also equally inhibited by low-grade ischemic preconditioning (18.2 +/- 10.6 IU/g dry weight, P <.05) and potassium cardioplegia (17.6 +/- 6.7 IU/g, P <.01) compared with control values. However, low-grade ischemic preconditioning in combination with potassium cardioplegia conferred no significant additional myocardial protection; left ventricular developed pressure was 80 +/- 17 mm Hg, and creatine kinase release was 14.8 +/- 11.0 IU/g. In contrast, high-grade ischemic preconditioning with potassium cardioplegia conferred better myocardial protection than potassium cardioplegia alone; left ventricular developed pressure was 121 +/- 16 mm Hg (P <.001), and creatine kinase release was 8.3 +/- 5.8 IU/g (P <.05). Chelerythrine itself had no significant effect on functional recovery and creatine kinase release in the control hearts, but it did inhibit the salutary effects not only of low-grade and high-grade ischemic preconditioning but also those of potassium cardioplegia. Low-grade ischemic preconditioning and potassium cardioplegia enhanced translocation of protein kinase C alpha to the membrane, whereas high-grade ischemic preconditioning also enhanced translocation of protein kinase C delta and epsilon. Chelerythrine inhibited translocation of all 3 protein kinase C isoforms. CONCLUSIONS: These results suggest that myocardial protection by low-grade ischemic preconditioning and potassium cardioplegia are mediated through enhanced translocation of protein kinase C alpha to the membrane. It is therefore suggested that activation of the novel protein kinase C isoforms is necessary to potentiate myocardial protection under potassium cardioplegia.

Animals↗

PubMed2001

Insulin-like growth factor 1 prevents neuronal cell death and paraplegia in the rabbit model of spinal cord ischemia.

OBJECTIVE: Insulin-like growth factor 1 has been shown to be cytoprotective against ischemia-reperfusion injury in various organs. However, spinal cord protection by insulin-like growth factor 1 has not been tested. We have therefore examined the effect of insulin-like growth factor 1 on neuronal cell death and motor function after spinal cord ischemia. METHODS: Japanese white rabbits were subjected to spinal cord ischemia by clamping the abdominal aorta for 15 minutes. Insulin-like growth factor 1 (0.3 mg/kg) at a dose equipotent to insulin (0.3 IU/kg) in lowering blood glucose level or the control (phosphate-buffered saline solution as a vehicle) was administered intravenously 30 minutes before the aortic clamp. RESULTS: Hind-limb motor function had recovered normally 48 hours after the operation in all the rabbits (n = 8) treated with insulin-like growth factor 1. In contrast, all the control-treated (n = 8) and all but one of the insulin-treated (n = 6) rabbits had deteriorated to paraplegia by 48 hours after the operation. Histopathologic sections in the involved spinal cord segment showed that a significantly (P <.0001) greater number of motor neuron cells were preserved in the rabbits treated with insulin-like growth factor 1 (17.9 +/- 4.8 per section) than in those treated with the control (8.0 +/- 2.1). Although insulin was equipotent to insulin-like growth factor 1 in preserving the number of motor neuron cells (18.5 +/- 2.7), the percentage of motor neuron cells positive for terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate-biotin nick-end labeling were significantly (P <.01) smaller in the rabbits treated with insulin-like growth factor 1 (6.0 +/- 4.6) compared with those treated with the control (54.6 +/- 33.8) and insulin (26.2 +/- 11.7). Immunohistochemical studies revealed that insulin-like growth factor 1 increased expression of the antiapoptotic Bcl-xL protein and inhibited expression of the proapoptotic Bax protein in motor neuron cells 24 and 48 hours after the operation. In contrast, expression of only Bax was increased after the operation in other groups of rabbits subjected to spinal cord ischemia. CONCLUSIONS: These results suggest that insulin-like growth factor 1, but not insulin with a conventional dose, protects motor neuron cells from ischemic spinal cord injury associated with differential regulation of Bcl-xL and Bax protein.

Animals↗

PubMed2001

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.

Adenosine Triphosphate↗

PubMed2001

Electromyographic evaluation of facial nerve damage in acoustic neuroma surgery.

OBJECTIVE: This study aimed to determine whether postoperative facial nerve paralysis or surgical manipulation causing paralysis could be predicted on train responses during intraoperative facial nerve monitoring in acoustic neuroma surgery. STUDY DESIGN AND SETTING: This was a prospective study performed at a tertiary referral center. PATIENTS AND METHODS: Train responses were recorded on a floppy disk and compared with postoperative facial nerve function in 51 patients who underwent enlarged translabyrinthine acoustic neuroma surgery. MAIN OUTCOME MEASURES: The number, duration, frequency, and peak-to-peak amplitude of train responses were analyzed and compared with postoperative facial nerve function. RESULTS: Trains were observed in 42 of 51 patients. Six of seven patients with high-amplitude trains more than 250 microV, and three of five patients with bomber-type high-frequency trains elicited during tumor dissection from the facial nerve or stretching the nerve, showed severe facial nerve dysfunction. On the other hand, seven of the nine patients with no trains also showed severe facial nerve dysfunction. CONCLUSIONS: The presence of high-amplitude or high-frequency trains elicited by surgical manipulation to the facial nerve seems to indicate a critical situation for the facial nerve. However, certain types of mechanical trauma resulting in severe facial nerve paralysis cannot be identified by train responses.

Adult↗

PubMed2001

Cubital tunnel release with lift-type endoscopic surgery.

A new technique of endoscopic release of the ulnar nerve at the elbow was designed for cubital tunnel syndrome. After three 5 mm incisions were made along the line of the ulnar nerve, the skin and subcutaneous tissue were lifted up using a fine tape to produce a provisional space. An endoscope was inserted through the one incision, and the constricting ligaments and fascia were released using a retrograde knife inserted through the other incision under endoscopic vision. Eight patients were treated using this method, and successful results were achieved. No neurovascular complications occurred, and all pre-operative complaints were resolved within three weeks. Our surgical series indicated an earlier return to work and daily activity due to early healing of incisions and minimal post-operative pain.

Adult↗

PubMed2001

Regional differences in mechanisms of cerebral circulatory response to neuronal activation.

Vibrissal stimulation raises cerebral blood flow (CBF) in the ipsilateral spinal and principal sensory trigeminal nuclei and contralateral ventroposteromedial (VPM) thalamic nucleus and barrel cortex. To investigate possible roles of adenosine and nitric oxide (NO) in these increases, local CBF was determined during unilateral vibrissal stimulation in unanesthetized rats after adenosine receptor blockade with caffeine or NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI). Caffeine lowered baseline CBF in all structures but reduced the percent increase during stimulation only in the two trigeminal nuclei. L-NAME and 7-NI lowered baseline CBF but reduced the percent increase during stimulation only in the higher stations of this sensory pathway, i.e., L-NAME in the VPM nucleus and 7-NI in both the VPM nucleus and barrel cortex. Combinations of caffeine with 7-NI or L-NAME did not have additive effects, and none alone or in combination completely eliminated functional activation of CBF. These results suggest that caffeine-sensitive and NO-dependent mechanisms are involved but with different regional distributions, and neither fully accounts for the functional activation of CBF.

Animals↗

PubMed2001

IGF-I differentially regulates Bcl-xL and Bax and confers myocardial protection in the rat heart.

Bcl-2 family proteins play a crucial role in the cytoprotective action of insulin-like growth factor-I (IGF-I) by regulating cell death signaling at the mitochondrial level. The present study examined the effect of IGF-I on the expression of Bcl-2 family proteins in the rat heart mitochondria in relation to myocardial protection against ischemia-reperfusion injury. Systemic IGF-I (1 mg) treatment in the rat increased Bcl-xL and attenuated Bax 12-24 h later in the heart mitochondria fraction. Permeability transition and cytochrome c release occurred in a Ca(2+) concentration-dependent manner in the vehicle-treated mitochondria. This was significantly inhibited by the IGF-I-pretreatment. Moreover, ATP synthesis was significantly greater in the IGF-I-pretreated mitochondria. IGF-I pretreatment 24 h before 25 min of global ischemia in the isolated rat heart model significantly improved recovery of isovolumic left ventricular function and inhibited creatine kinase release during reperfusion. This was associated with a significantly less number of terminal transferase labeling-positive myocytes and nonmyocytes 2 h after reperfusion. These results suggest that IGF-1 differentially regulates Bcl-xL and Bax in heart mitochondria, which may be causally related to myocardial protection against ischemia-reperfusion injury.

Adenosine Triphosphate↗

PubMed2001

NHE and ICAM-1 expression in hypoxic/reoxygenated coronary microvascular endothelial cells.

Although Na+/H+ exchange (NHE) has been implicated in myocardial reperfusion injury, participation of coronary microvascular endothelial cells (CMECs) in this pathogenesis has been poorly understood. NHE-induced intracellular Ca2+ concentration ([Ca2+]i) overload in CMECs may increase the synthesis of intercellular adhesion molecules (ICAM), which is potentially involved in myocardial reperfusion injury. The present study tested the hypothesis that NHE plays a crucial role in [Ca2+]i overload and ICAM-1 synthesis in CMECs. Primary cultures of CMECs isolated from adult rat hearts were subjected to acidic hypoxia for 30 min followed by reoxygenation. Two structurally distinct NHE inhibitors, cariporide and 5-(N-N-dimethyl)-amiloride (DMA), had no significant effect on the acidic hypoxia-induced decrease in intracellular pH (pH(i)) of CMECs but significantly retarded pH(i) recovery after reoxygenation. These NHE inhibitors abolished the hypoxia- and reoxygenation-induced increase in [Ca2+]i. Expression of ICAM-1 mRNA was markedly increased in the vehicle-treated CMECs 3 h after reoxygenation, and this was significantly inhibited by treatment with cariporide, DMA, or Ca2+-free buffer. In addition, enhanced ICAM-I protein expression on the cell surface of CMECs 8 h after reoxygenation was attenuated by treatment with cariporide, DMA, or Ca2+-free buffer. These results suggest that NHE plays a crucial role in the rise of [Ca2+]i and ICAM-1 expression during acidic hypoxia/reoxygenation in CMECs. We propose that inhibition of ICAM-1 expression in CMECs may represent a novel mechanism of action of NHE inhibitors against ischemia-reperfusion injury.

Amiloride↗

PubMed2001

Coronary artery bypass grafting within 30 days of an acute myocardial infarction.

UNLABELLED: Early surgical intervention is now often considered for symptomatic patients after an acute myocardial infarction. Conversely coronary artery bypass grafting soon after an acute myocardial infarction poses substantial risks. The present study was performed to evaluate the results of Coronary artery bypass grafting soon after an acute myocardial infarction. METHODS: From November 1991 to November 1999, 478 consecutive patients underwent coronary artery bypass grafting and 68 of these underwent an operation within 30 days of AMI. The data of these patients were analyzed retrospectively. Univariate and multivariate analyses of many variables were performed regarding operative mortality. RESULTS: Operative mortality (7.4%) was significantly higher in the patients with an acute myocardial infarction than in the patients without it (0.8%) during the same period as the subjects of this study. Coronary artery bypass grafting without arterial grafts was solely determined to be the predictor of survival. The survival curve demonstrated better long-term results in patients undergoing bypass grafting with arterial grafts than in patients undergoing bypass grafting with venous grafts alone. CONCLUSIONS: If hemodynamic conditions can not be stabilized, then coronary artery bypass grafting using arterial grafts, when indicated, should be performed even early after AMI.

Acute Disease↗

PubMed2001

[CD13- and CD33-negative acute myelocytic leukemia (FAB classification; M2) with morphological changes and CD13 expression on recurrence].

A 42-year-old man was diagnosed as having acute myelocytic leukemia in July 1998. The leukemic cells tended to be differentiated, and on the basis of positive peroxidase staining, this case was considered to be AML (M2) according to the FAB classification. t(8;21)(q22;q22) chromosomal abnormality was observed, but surface antigen analysis revealed no expression of either CD13 or CD33, a finding characteristic of myelocytic leukemia. Combination chemotherapy resulted in complete remission, and allogeneic bone marrow transplantation was performed with donor cells from the patient's sister. Unfortunately, however, the patient died about 18 months after the onset of leukemia. Comparison of the findings at recurrence with those at initial diagnosis revealed morphological changes in non-differentiated immature cells (AML-M1) and CD13 surface antigen expression. This was considered to be a rare case of AML with neither CD13 nor CD33 expression at onset, but with CD13 expression at recurrence.

Adult↗

PubMed2001

[Influential factors in the elevation of serum creatine phosphokinase for the patients with Kanemi Yusho--freeze fracture study of rat muscle plasma membrane].

We studied the factors of the elevation of serum creatine phosphokinase (CK) using the data from the routine medical checkup of Kanemi Yusho patients during 1995 and 1999. We also studied rat muscle plasma membrane by the freeze fracture method, which were given the polychlorinated biphenyls (PCB) and controls. The patients with elevation of serum CK showed significant elevation of PCB in their blood but not in polychlorinated quanterphenyls (PCQ). The rat muscle plasma membrane showed a slight increase of orthognal array density but it was not statistically significant. The densities of caveolae and particles were not changed. Accordingly, PCB were thought to be a factor in the elevation of CK in the serum.

Animals↗

PubMed2000

Vacuolar H(+)-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts in cultured human saphenous vein.

BACKGROUND: The molecular mechanism of neointimal hyperplasia after vein graft surgery remains elusive. Vacuolar H(+)-ATPase (V-ATPase) is involved in intracellular trafficking and may play a crucial role in neointimal cell growth. METHODS AND RESULTS: Cultured human saphenous vein segments developed neointimal formation within 10 days. Neointimal cells were positive for vimentin and alpha-smooth muscle actin but negative for desmin, which is indicative of myofibroblasts. Those myofibroblasts were found to have originated from periadventitial fibroblasts, which upregulated the expression of 16-kDa proteolipid of V-ATPase before proliferation and phenotypic modulation. Neointimal myofibroblast growth and survival were highly sensitive to inhibition of V-ATPase by bafilomycin A(1) (BA(1)), because the incorporation of [(3)H]thymidine into the myofibroblasts was significantly inhibited by nanomolar concentrations of BA(1) and apoptotic cell death was induced by a similar concentration range of BA(1). In contrast, endothelial cells and differentiated smooth muscle cells were resistant to apoptosis by BA(1). CONCLUSIONS: These results suggest that V-ATPase plays a crucial role in growth and phenotypic modulation of myofibroblasts that contributes to neointimal formation in cultured human saphenous vein.

Adult↗

PubMed2000

Mechanistic aspects of palladium-catalyzed allylstannylation of alkynes

An alpha-methylallylstannane added to an alkyne in the presence of a palladium catalyst with perfect regioselectivity both in the allylic and alkynic moieties. Comparison of the reaction of isomeric butenylstannanes suggests two catalytic cycles, one of which includes a palladacyclopentene intermediate and beta-tin elimination pathway.

Journal Article↗

PubMed2000

Positive reactions to common allergens in 42 atopic dogs in Japan.

Clinically important allergens for the diagnosis and treatment of atopic dermatitis vary geographically. In order to identify the most prevalent allergens in atopic dogs in Japan, 42 dogs with a clinical diagnosis of atopy were tested using both in vivo (intradermal skin test (IDST)) and in vitro (antigen-specific IgE assay) allergy tests. Allergens used for IDST included 26 allergen extracts from eight allergen groups: trees, weeds, grasses, house dust mites (HDM), molds, foods, epithelia, and arthropods. Immunodot assay was used to measure antigen-specific IgE against 24 allergens from these eight groups and against fish such as cod and sole. In the 42 dogs, the most common positive allergen reaction was to HDM on both IDST (29/42 dogs or 69%) and in vitro testing (23/42 or 54.8%). The second most frequent positive allergen reaction was to Japanese cedar pollen (21/42 or 50.0% for IDST and 7/42 or 16.7% for in vitro testing). In both tests, less than 20% of dogs had positive reactions to molds or foods. Positive reactions to cat epithelia were frequently found on IDST, but rarely found on in vitro testing. Agreement between the two tests was found in 26 instances: HDM (21 dogs), Japanese cedar pollen (five dogs) and wheat (one dog). In this study, the two most common allergens involved in atopic dermatitis in dogs in Japan were HDM and Japanese cedar pollen.

Allergens↗

PubMed2000

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.

Animals↗

PubMed2000

Fiber-in-tube solid-phase microextraction: a fibrous rigid-rod heterocyclic polymer as the extraction medium.

A novel "fiber-in-tube" configuration has been applied to the extraction tube of solid phase microextraction (SPME), and the direct coupling of the extraction process to liquid chromatography (LC) has been accomplished for the analysis of n-butylphthalate in wastewater. By using this fiber-in-tube SPME/LC system the preconcentration factor for the phthalate was about 160 with 20 min extraction and no interference peak was observed in the chromatogram. The results also showed the potential applications of this fiber-in-tube SPME/LC for the analysis of sub-ppb level (i.e., lower than 1 ng/mL) of various organic analytes in aqueous sample matrix without a large solvent consumption during the preconcentration process.

Journal Article↗

PubMed2000

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.

Animals↗

PubMed2000

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.

Androstadienes↗