Biomedical subjects

Jianhua Cui

Publications and source records attributed to Jianhua Cui.

18 recordsLinked to original sources

PubMed2006

Generation of survival signal by differential interaction of p38MAPKalpha and p38MAPKbeta with caveolin-1 and caveolin-3 in the adapted heart.

Sphingomyelin breakdown product ceramide has recently been found to induce an adaptive response and reduce myocardial ischemia/reperfusion injury. Since activation of MAP kinases plays an essential role in myocardial adaptation to ischemic stress and since ceramide is involved in lipid raft formation where MAP kinases can be translocated in response to stress, we reasoned that preconditioning may potentiate the translocation of MAP kinases into the lipid raft. To test the hypothesis, rats were divided into five groups: (i) control, (ii) ischemia/reperfusion (I/R), (iii) I/R+C-2 ceramide, (iv) adapted and (v) adapted+desipramine, an inhibitor of ceramide formation. Isolated hearts were preperfused for 15 min with Krebs Henseleit bicarbonate (KHB) buffer in the absence or presence of 10 microM desipramine followed by adaptation induced by four cyclic episodes of 5 min ischemia and 10 min reperfusion. For myocardial adaptation to ischemia with ceramide, the hearts were perfused with 1 microM C-2 ceramide. All hearts were then subjected to 30 min ischemia and 2 h of reperfusion. As expected, both ischemic adaptation and ceramide adaptation made the heart resistant to I/R injury as evidenced by improved ventricular performance and reduced myocardial infarct size and cardiomyocyte apoptosis, which were significantly blocked with desipramine indicating the involvement of ceramide in ischemic adaptation. Ceramide also participated in the formation of lipid raft, and desipramine disrupted the raft formation. In the adapted hearts, there was an increased association of the proapoptotic p38MAPKalpha with caveolin-1 while there was a reduced association of anti-apoptotic p38MAPKbeta with caveolin-3 indicating reduced amount of p38MAPKalpha and increased amount of p38MAPKbeta were available to the adapted hearts thereby generating a survival signal. Desipramine decreased the association of P38MAPKalpha and C-2 ceramide increased the association of P38MAPKalpha with the lipid raft. The survival signal was further confirmed by increased phosphorylation of AKT and enhanced induction of expression of Bcl-2 during adaptation and its reversal with desipramine. The results indicated a unique ceramide signaling the ischemic and PC hearts involving lipid rafts, which generated a survival signal by differentially associating the p38MAPKalpha and p38MAPKbeta with the caveolin-1 and caveoli-3, respectively.

Adaptation, Physiological↗

PubMed2006

Cooperation between VEGF and beta3 integrin during cardiac vascular development.

In the developing myocardium, vascular endothelial growth factor (VEGF)-dependent neovascularization occurs by division of existing vessels, a process that persists for several weeks following birth. During this remodeling phase, mRNA expression of beta3 integrin in the heart decreases significantly as vessel maturation progresses. However, in male mice lacking beta3, coronary capillaries fail to mature and continue to exhibit irregular endothelial thickness, endothelial protrusions into the lumen, and expanded cytoplasmic vacuoles. Surprisingly, this phenotype was not seen in female beta3-null mice. Enhanced VEGF signaling contributes to the beta3-null phenotype, because these vessels can be normalized by inhibitors of VEGF or Flk-1. Moreover, intravenous injection of VEGF induces a similar angiogenic phenotype in hearts of adult wild-type mice. These findings show a clear vascular phenotype in the hearts of mice lacking beta3 and suggest this integrin plays a critical role in coronary vascular development and the vascular response to VEGF.

Animals↗

PubMed2006

Comparison of cardioprotective abilities between the flesh and skin of grapes.

Recent studies have documented that grapes and grape juices are equally cardioprotective as red wine. The existing reports implicate that the skin and seeds of the grapes containing polyphenolic antioxidants are instrumental for the cardioprotective properties of grapes. The present study examines if the flesh of grapes also possesses any cardioprotective abilities. Three groups of randomly selected rats were fed, water only (control), flesh of the grapes (2.5 mg/kg b. wt.) or the skins (2.5 mg/kg b. wt.) for 30 days. At the end of the 30 days, isolated perfused hearts were made ischemic for 30 min followed by 2 h of reperfusion in the working mode. The results demonstrated that both flesh and skin of the grapes could protect the hearts from ischemic reperfusion injury as evidenced by improved postischemic ventricular recovery and reduced myocardial infarct size. High performance liquid chromatography (HPLC) revealed that skin and flesh contained comparative amounts of glucose, fructose, tartaric acid, malic acid, shikimic acid, and trans-caftaric acid. In addition, the flesh contained reduced amounts (compared to skin) of cis-coutaric, trans-coutaric, caffeic, p-coumaric, cinnamics, and catechin/epicatechin. Total polyphenolic index was also lower in flesh compared to skin. The anthocyanins were present exclusively in the skin. Electron paramagnetic resonance (EPR) spectrometry of hydroxy radicals indicated that both flesh and skins possessed equal amount of ROS scavenging activities. Total malonaldehyde content in the heart was reduced comparatively with either flesh or skin. The results indicate for the first time that the flesh of grapes are equally cardioprotective as skin, and antioxidant potential of skin and flesh of grapes are comparable with each other despite of the fact that flesh does not possess any anthocyanin activities.

Animals↗

PubMed2005

Role of lipid rafts in ceramide and nitric oxide signaling in the ischemic and preconditioned hearts.

Nitric oxide plays a crucial role in myocardial ischemia reperfusion injury as well as in myocardial adaptation to ischemic stress. To understand the dichotomy of nitric oxide behavior in the ischemic myocardium, isolated rat hearts were subjected to ischemia/reperfusion protocol. The tissue contents of sphingomyelin (SM), ceramide and sphingosine were determined by high performance thin layer chromatography (HPTLC). The myocardial plasma proteins were immunoprecipitated with caveolin-1 specific antibody. Ischemia/reperfusion resulted in the breakdown of SM with corresponding accumulation of ceramide and sphingosine. Immunoprecipitation with eNOS-specific antibody revealed the association of eNOS with caveolin-1 fraction of the heart. Ischemia/reperfusion caused a depression of contractile function and an increased apoptotic cell death and myocardial infarct size, which were reversed by pre-perfusing the hearts with desipramine, an sphingomyelinase inhibitor that also prevented ceramide accumulation and eNOS association with caveolin-1. The similar results were obtained when the hearts were adapted to ischemic stress by subjecting them to repeated reversible ischemia and reperfusion. The results indicate that ischemia/reperfusion causes an increase in eNOS, which is unavailable to the ischemic heart because of its binding with caveolin-1. Ceramide plays a crucial role in this process, because prevention of ceramide formation either by myocardial adaptation to ischemia or with desipramine results in the inhibition of eNOS association with caveolin-1 thereby reducing myocardial ischemic reperfusion injury.

Animals↗

PubMed2005

Extracellular matrix scaffold for cardiac repair.

BACKGROUND: Heart failure remains a significant problem. Tissue-engineered cardiac patches offer potential to treat severe heart failure. We studied an extracellular matrix scaffold for repairing the infarcted left ventricle. METHODS AND RESULTS: Pigs (n=42) underwent left ventricular (LV) infarction. At 6 to 8 weeks, either 4-layer multilaminate urinary bladder-derived extracellular matrix or expanded polytetrafluoroethlyene (ePTFE) was implanted as full-thickness LV wall patch replacement. At 1-week, 1-month, or 3-month intervals, pigs were terminated. After macroscopic examination, samples of tissue were prepared for histology, immunocytochemistry, and analysis of cell proportions by flow cytometry. One-week and 1-month patches were intact with thrombus and inflammation; at 1 month, there was also tissue with spindle-shaped cells in proteoglycan-rich and collagenous matrix. More alpha-smooth muscle actin-positive cells were present in urinary bladder matrix (UBM) than in ePTFE (22.2+/-3.3% versus 8.4+/-2.7%; P=0.04). At 3 months, UBM was bioresorbed, and a collagen-rich vascularized tissue with numerous myofibroblasts was present. Isolated regions of alpha-sarcomeric actin-positive, intensely alpha-smooth muscle actin-immunopositive, and striated cells were observed. ePTFE at 3 months had foreign-body response with necrosis and calcification. Flow cytometry showed similarities of cells from UBM to normal myocardium, whereas ePTFE had limited cardiomyocyte markers. CONCLUSIONS: Appearance of a fibrocellular tissue that included contractile cells accompanied biodegradation of UBM when implanted as an LV-free wall infarction patch. UBM appears superior to synthetic material for cardiac patching and trends toward myocardial replacement at 3 months.

Absorbable Implants↗

PubMed2004

Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis.

VEGF is unique among angiogenic growth factors because it disrupts endothelial barrier function. Therefore, we considered whether this property of VEGF might contribute to tumor cell extravasation and metastasis. To test this, mice lacking the Src family kinases Src or Yes, which maintain endothelial barrier function in the presence of VEGF, were injected intravenously with VEGF-expressing tumor cells. We found a dramatic reduction in tumor cell extravasation in lungs or livers of mice lacking Src or Yes. At the molecular level, VEGF compromises the endothelial barrier by disrupting a VE-cadherin-beta-catenin complex in lung endothelium from wild-type, but not Yes-deficient, mice. Disrupting the endothelial barrier directly with anti-VE-cadherin both amplifies metastasis in normal mice and overcomes the genetic resistance in Yes-deficient mice. Pharmacological blockade of VEGF, VEGFR-2, or Src stabilizes endothelial barrier function and suppresses tumor cell extravasation in vivo. Therefore, disrupting Src signaling preserves host endothelial barrier function providing a novel host-targeted approach to control metastatic disease.

Animals↗

PubMed2004

Role of ceramide in ischemic preconditioning.

BACKGROUND: A recent study showed increased myocardial content of ceramide and sphingosine during preconditioning (PC). Because sphingosine-1-phosphate, a metabolite of ceramide, may function as an antiapoptotic factor, we hypothesized the increased ceramide during PC may be heart's effort to harness its own protection. STUDY DESIGN: The isolated hearts were divided into five groups: 1) perfused for 3 hours 45 minutes with KHB buffer (control); 2) perfused with buffer for 45 minutes followed by 30 minutes of ischemia and 2 hours of reperfusion; 3) perfused for 15 minutes with desipramine followed by 30 minutes of perfusion with buffer, 30 minutes of ischemia, and 2 hours of reperfusion; 4) preconditioned followed by 30 minutes of ischemia and 2 hours of reperfusion; and 5) the same as 4), but preperfused for 15 minutes with desipramine. Myocardial preservation was assessed by examining left ventricular function, infarct size, and cardiomyocyte apoptosis. RESULTS: Ischemia/reperfusion-mediated cardiac dysfunction was partially restored with desipramine. PC improved postischemic ventricular recovery and reduced myocardial infarct size and cardiomyocyte apoptosis. The cardioprotective abilities of PC were abolished with desipramine, which also downregulated a PC-mediated increase in antiapoptotic protein Bcl-2. The apparent paradoxical results of desipramine can be explained by the increase in proapoptotic ceramide content in the ischemic reperfused heart that was blocked with desipramine and an increase in antiapoptotic sphingosine-1-p content in the preconditioned heart that was inhibited with desipramine. CONCLUSIONS: The results suggested for the first time that sphingolipid can induce the expression of Bcl-2 warranting its clinical use as a pharmacologic PC agent.

Animals↗

PubMed2004

Impact of intraaortic balloon counterpulsation on arterial blood flow in juvenile pigs with heart failure.

OBJECTIVES: To assess the impact of intraaortic balloon counterpulsation on coronary, renal and aortic blood flow in an animal heart failure model. BACKGROUND: Heart failure exacerbations are still often treated with inotropic medications despite a lack of evidence demonstrating any benefit with these drugs. Intraaortic balloon counterpulsation may be considered in certain cases a bridge to recovery. METHODS: Four juvenile pigs underwent pacemaker implantation to induce a rapid-pacing mediated dilated cardiomyopathy. After approximately 4 weeks of rapid pacing, the mean ejection fraction was reduced to 28.8+/-9.5% with a mean systolic blood pressure of 64/44 mmHg. The pigs then underwent surgical placement of flow probes around the circumflex coronary artery, renal artery and infrarenal aorta. A Millar catheter was used to calculate Dp/Dt and a Swan-Ganz to calculate cardiac output. Data were recorded at baseline and after 10 minutes of balloon pumping. The pigs were euthanized post-procedure. RESULTS: Coronary blood flow was increased 9.7% by balloon counterpulsation from 38.3 +/- 12.0 to 42.0+/-11.4 ml/s (p=NS). Renal blood flow was reduced 11.9% by counterpulsation from 130.0+/-88.6 ml/s to 114.5+/-76.6 ml/s (p=NS). Infrarenal aortic blood flow was not changed (mean of 900 ml/s with and without counterpulsation); blood pressure, cardiac output and Dp/Dt were not changed after 10 minutes of pumping. There was little impact observed by changing the position of the balloon closer to or farther away from the apex of the aortic arch. CONCLUSION: Intraaortic balloon counterpulsation did not significantly improve hemodynamics in the pig heart failure model. This may be attributed to the high compliance of the juvenile pig's aorta, thus attenuating the pressure wave generated by counterpulsation. A larger volume balloon would merit investigation for this application.

Animals↗

PubMed2003

Effects of L-carnitine and its derivatives on postischemic cardiac function, ventricular fibrillation and necrotic and apoptotic cardiomyocyte death in isolated rat hearts.

The study aimed to examine whether L-carnitine and its derivatives, acetyl-L-carnitine and propionyl-L-carnitine, were equally effective and able to improve postischemic cardiac function, reduce the incidence of reperfusion-induced ventricular fibrillation, infarct size, and apoptotic cell death in ischemic/reperfused isolated rat hearts. There are several studies indicating that L-carnitine, a naturally occurring amino acid and an essential cofactor, can improve mechanical function and substrate metabolism not only in hypertrophied or failing myocardium but also in ischemic/reperfused hearts. The effects of L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine, on the recovery of heart function, incidence of reperfusion-induced ventricular fibrillation (VF), infarct size, and apoptotic cell death after 30 min ischemia followed by 120 min reperfusion were studied in isolated working rat hearts. Hearts were perfused with various concentrations of L-carnitine (0.5 and 5 mM), acetyl-L-carnitine (0.5 and 5 mM), and propionyl-L-carnitine (0.05, 0.5, and 5 mM), respectively, for 10 min before the induction of ischemia. Postischemic recovery of CF, AF, and LVDP was significantly improved in all groups perfused with 5 mM of L-carnitine, acetyl-L-carnitine, and propionyl-L-carnitine. Significant postischemic ventricular recovery was noticed in the hearts perfused with 0.5 mM of propionyl-L-carnitine, but not with the same concentration of L-carnitine or L-acetyl carnitine. The incidence of reperfusion VF was reduced from its control value of 90 to 10% (p < 0.05) in hearts perfused with 5 mM of propionyl-L-carnitine only. Other doses of various carnitines failed to reduce the incidence of VF. The protection in CF, AF, LVDP, and VF reflected in a reduction in infarct size and apoptotic cell death in hearts treated with various concentrations of carnitine derivatives. The difference between effectiveness of various carnitines on the recovery of postischemic myocardium may be explained by different membrane permeability properties of carnitine and its derivatives.

Acetylcarnitine↗

PubMed2003

Vasomotor function of pig coronary arteries after chronic coronary occlusion.

Placement of an ameroid constrictor in large-conduit pig coronary arteries causes progressive stenosis and distal myocardial ischemia. Blood perfusion in the ischemic region is partly dependent on vasomotor responses to neural and humoral factors distal to the occlusion site. To ascertain the degree of impairment of vascular function in pigs, the authors induced myocardial ischemia by placing an ameroid constrictor in the left circumflex coronary artery and examined vascular reactivity and histopathology distal to the constriction site. The sensitivity of the distal left circumflex coronary and nonoccluded control left anterior descending arteries to PGF(2alpha) was similar. After nitric oxide blockade using Nw-nitro-l-arginine methylester (l-NAME), the sensitivity and maximal contraction to PGF(2alpha) were significantly increased in both the left circumflex coronary (EC50: 5.86 +/- 0.74 vs. 3.28 +/- 0.84 microM; C(max): 4.63 +/- 0.28 vs. 6.25 +/- 0.30 g, P < 0.01) and left anterior descending (EC50: 6.57 +/- 0.73 vs. 2.78 +/- 0.16 microM; C(max): 5.09 +/- 0.37 vs. 6.95 +/- 0.39 g, P < 0.01) arteries. Substance P-induced relaxation (100 pM) was blocked to a larger degree in the distal left circumflex coronary artery when compared with the left anterior descending artery (76.9 +/- 4.2% vs. 56.4 +/- 3.1%, P < 0.05). Endothelium-independent relaxation to sodium nitroprusside was similar in the left circumflex coronary and left anterior descending arteries before and after nitric oxide blockade. Histopathologic examination showed no major differences between distal left circumflex coronary artery segments and left anterior descending artery controls. However, scanning electron microscopy showed endothelial hypertrophy and activation in specimens from the left circumflex coronary arteries. In summary, as a result of the major hemodynamic changes induced by a chronic constriction and eventual occlusion of a large coronary artery, distal segments underwent adaptive compensatory changes. Such compensation may be related to an increased nitric oxide production by the hypertrophic endothelium in response to alterations in coronary hemodynamics.

Animals↗

PubMed2002

Cardioprotection with grapes.

Epidemiologic studies suggest that mild-to-moderate wine consumption is associated with a reduced incidence of mortality and morbidity from coronary heart disease. Because wines are produced from grapes, this study was done to determine whether the grapes were equally cardioprotective. Sprague-Dawley male rats were given (orally) standardized grape extract (SGE) (obtained from the California Table Grape Commission, Fresno, CA, U.S.A.) (50, 100, or 200 mg/kg body weight per day) for 3 weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 g of glucose plus 45 microg/100 g of fructose per day for 3 weeks. After 21 days, rats were killed and the hearts excised and perfused via working mode. Hearts were made ischemic for 30 min followed by 2 h of reperfusion. At 100 mg/kg and at 200 mg/kg, grapes provided significant cardioprotection as evidenced by improved postischemic ventricular recovery (aortic flow, developed pressure, the maximum first derivative of the developed pressure) and reduced amount of myocardial infarction. There were no differences in results between the two groups (100 mg/kg versus 200 mg/kg). No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/d. SGE reduced the malonaldehyde content of the heart, indicating reduction of oxidative stress during ischemia and reperfusion. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals that are formed in the ischemic reperfused myocardium. The results demonstrate that the hearts of the rats fed SGE are resistant to myocardial ischemia reperfusion injury, suggesting a cardioprotective role of grapes.

Animals↗

PubMed2002

Reduction of myocardial ischemia reperfusion injury with regular consumption of grapes.

Recently several polyphenolic antioxidants derived from grape seeds and skins have been implicated in cardioprotection. This study was undertaken to determine if the grapes were equally cardioprotective. Sprague Dawley male rats were given (orally) standardized grape extract (SGE) for a period of three weeks. Time-matched control experiments were performed by feeding the animals 45 microg/100 of glucose plus 45 microg/100 g fructose per day for three weeks. After 30 days, rats were sacrificed, hearts excised and perfused via working-mode. Hearts were made ischemic for 30 min followed by two hours of reperfusion. At 100 mg/kg and at 200 mg/kg, SGE provided significant cardioprotection as evidenced by improved post-ischemic ventricular recovery and reduced amount of myocardial infarction. No cardioprotection was apparent when rats were given grape samples at a dose of 50 mg/100 g/day. In vitro studies demonstrated that the SGE could directly scavenge superoxide and hydroxyl radicals which are formed in the ischemic reperfused myocardium. The results demonstrate that the heats of the rats fed SGE reduced myocardial ischemia reperfusion injury by functioning as in vivo antioxidant.

Animals↗

PubMed2002

Cardioprotective abilities of white wine.

To study if white wines, like red wine, can also protect the heart from ischemia reperfusion injury, ethanol-free extracts of three different white wines (WW1, WW2 and WW3) (100 mg/100 g body weight) were given orally to Sprague Dawley rats (200 g body weight) for three weeks. Control rats were given water only for the same period of time. After three weeks, rats were anesthetized and sacrificed, and the hearts excised for the preparation of isolated working rat heart. All hearts were subjected to 30 min global ischemia followed by two hours of reperfusion. The results demonstrated that among the three different white wines, only WW2 showed cardioprotection as evidenced by improved post-ischemic ventricular recovery compared to control. The amount of malonaldehyde production in white wine-fed rat hearts were lower compared to that found in control hearts indicating reduced formation of the reactive oxygen species. In vitro studies using chemiluminescence technique revealed that these white wines scavenged both superoxide anions and hydroxyl radicals. The results of our study demonstrated that only WW2 white wine provided cardioprotection as evidenced by the improved the post-ischemic contractile recovery and reduced myocardial infarct size. The cardioprotective effect of this white wine may be attributed, at least in part, from its ability to function as an in vivo antioxidant.

Animals↗

PubMed2002

[The effect of rhodiola and acetazolamide on the sleep architecture and blood oxygen saturation in men living at high altitude].

OBJECTIVE: To study the changes of sleep architecture and blood oxygen saturation (SaO(2)) during sleep in men living at high altitude, and to investigate the effect of rhodiola and acetazolamide on these sleep indexes. METHODS: Twenty-four men aged 18 to 21 years who had stayed at high altitude (5 380 m above sea level) for 1 year were randomly divided into groups A (treated with oral rhodiola), B (treated with oral acetazolamide) and C (treated with rhodiola + acetazolamide). Their sleep architecture and SaO(2) were recorded for 24 days before and after taking the medicines. RESULTS: Compared with baseline, the waking SaO(2) (WSaO(2)), the lowest SaO(2) (LSaO(2)) and the mean SaO(2) (MSaO(2)) were increased significantly after treatment for 24 days (P < 0.01), and the times of oxygen desaturation >/= 4% per hour (DI4) and the percentage of time spent at SaO(2) below 80% (SIT(80)) were decreased significantly (P < 0.01). After treatment, the NREM I and II was shortened, and III + IV and REM sleep were prolonged (P < 0.01): the total waking time (TWT) was shortened, and the sleep efficiency index (SEI) was markedly increased (P < 0.01). Compared with group A's, groups B's and C's SIT(80) were increased (P < 0.05). CONCLUSION: Both rhodiola and acetazolamide were effective in modulating the sleep architecture and improving the sleep quality in young men living at high altitude, but there was no synergistic effect between rhodiola and acetazolamide.

Acetazolamide↗

PubMedDate not supplied

A clinically relevant large-animal model for evaluation of tissue-engineered cardiac surgical patch materials.

Extracellular matrix (ECM) scaffolds may be useful as a tissue engineering approach toward myocardial regeneration in the infarcted heart. An appropriate large-animal model for testing the utility of biologically derived ECM in this application is needed. The purpose of this study was to develop such a model for optimal procedural success during and after patch implantation surgery. Myocardial infarction (MI) was created by embolization of the diagonal artery (DA) branch of the left anterior descending coronary artery with collagen suspension. After 4 to 6 weeks, 14 pigs received patch implant (ECM or expanded polytetrafluoroethylene). Six pigs were infarcted in the first DA and seven pigs in the second DA. Electrophysiology study was performed within 3 days before surgery. During surgery, the size and location of the infarct were measured. Infarcted myocardium (1.5-cm diameter) was transmurally excised under partial cardiopulmonary bypass. Patches (3-cm diameter) were sutured to the endomyocardial defect. Four pigs died postoperatively. After 1 month, 10 pigs were euthanized and the locations of patches were examined. Success rate of patch implant in the second DA (85.7%) was higher than the first DA (50%) group. Infarct size in the second DA was smaller than in the first DA (4.6+/-1.2 vs. 10.8+/-2.4 cm(2), P<.05). The second DA was more anteriorly positioned, which enabled easier access from the midsternal thoracotomy. However, the first DA was more laterally located requiring more manipulation of the heart during surgery. Electrophysiology revealed no ventricular tachyarrhythmia in the second DA but 33.3% in the first DA group (P<.05). At necropsy, the endocardial position of the first DA-infarct patches was anteroapical, whereas the second DA-infarct patches were more basolateral and often involved the anterior papillary muscle. The success rate of patch implant was associated with infarction size and location, and may be related to arrhythmic substrate. Experimental MI created by the second DA embolization is a feasible model for investigation of tissue-engineered cardiac patch implantation. This large-animal model is also suitable for study of cell therapy via endocardial catheter-based approaches or open surgical methods.

Animals↗

PubMedDate not supplied

Safety of intramyocardial injection of autologous bone marrow cells to treat myocardial ischemia in pigs.

OBJECTIVE: The purpose of this study is to determine the potential adverse consequences of intracardiac injections of bone marrow mononuclear cells (BMCs) to facilitate the revascularization of ischemic myocardium. BACKGROUND: Bone marrow mononuclear cells are used to treat heart failure, though there are few studies that evaluated the safety of BMC transplantation for chronic myocardial ischemia. METHODS: The pigs received coronary ameroid constrictors to induce chronic myocardial ischemia and left ventricular dysfunction. At 4 weeks, autologous BMCs were injected intramyocardially by Boston Scientific Stiletto catheter with low-dose (10(7) cells) or high-dose BMC (10(8)). Control animals received saline. Blood samples were collected for hematological and chemical indices, including cardiac enzyme levels at regular time intervals postinfarction. At 7 weeks, animals underwent electrophysiological study to evaluate the arrhythmic potential of transplanted BMC, followed by necropsy and histopathology. RESULTS: No mortalities were associated with intramyocardial delivery of BMC or saline. At Day 0, the total creatine phosphokinase (CPK) was in the normal range in all groups. All groups had significant elevations in CPK after ameroid placement, with no significant differences between groups. At 7 weeks, CPK in all groups had returned to pretreatment levels. Electrophysiological assessment revealed that one control animal had an inducible arrhythmia. No arrhythmias were induced in low- or high-dose BMC-treated pigs. There were no histopathological changes associated with BMC injection. CONCLUSION: This study showed, in a clinically relevant large-animal model, that catheter-based intramyocardial injection of autologous BMC into ischemic myocardium is safe.

Animals↗

PubMedDate not supplied

Endovascular irradiation impairs vascular functional responses in noninjured pig coronary arteries.

PURPOSE: To assess the effects of endovascular irradiation on vascular structure and function in pig coronary arteries in the absence of vascular injury. METHODS AND MATERIALS: Vasomotor responses to contractions of KCl and prostaglandin F2alpha (PGF2alpha), relaxations to endothelium-dependent (substance P, A23187) and -independent (sodium nitroprusside, SNP) agents; endothelial morphology and superoxide anion (02*-) production were investigated in control (naive), sham and irradiated (20 Gy, 32P) arteries 1 month after irradiation. RESULTS: Contractions to KCl and PGF2alpha in the presence of L-NAME were significantly decreased, relaxations to substance P and A23187 were abolished and SNP-induced relaxation was potentiated in irradiated arteries compared to naive and sham-treated vessels. Scanning electron microscopy (SEM) revealed enlarged endothelial cells (ECs) exhibiting surface microvilli. O2*- production was significantly increased in irradiated vessels (437.0 +/- 37.3 vs. 126.0 +/- 11.6 RLU/s/mg tissue, P < .01). CONCLUSIONS: One month after brachytherapy, normal pig coronary arteries showed abnormal vascular reactivity, altered endothelial morphology and increased production of O2*-. Lack of relaxation to substance P and A23187 reflects ionizing radiation-mediated damage to ECs, whereas potentiation of relaxation to SNP suggests additional deleterious effects on medial smooth muscle cells (SMCs). Increased O2*- production might have contributed to endothelial dysfunction by scavenging nitric oxide (NO).

Angioplasty↗

PubMedDate not supplied

Distal endothelial function and vascular morphology after catheter-based radiation in pig coronary arteries.

PURPOSE: Endovascular irradiation inhibits neointimal hyperplasia in ballooned and stented arteries but impacts both diseased and adjacent normal tissue. Little is known about the effects of irradiation on downstream vasculature. In this study, we investigated vascular function and structure of pig coronary arteries distal to sites of endoluminal irradiation. MATERIALS AND METHODS: Vasomotor responses of distal arteries to contraction of KCl and PGF2alpha and endothelium-dependent (substance P and A23187) and -independent (sodium nitroprusside) relaxation were studied in naïve, sham-treated, irradiated, stented, and stented plus irradiated vessels. Light and scanning electron microscopy were used to assess vascular morphology. RESULTS: Relaxations to substance P and A23187 at 1 month post treatment were significantly decreased in the irradiated group, whereas contractile response to PGF2alpha was significantly increased. Hemorrhage, mural thrombus, and inflammation were present at the upstream-irradiated site; inflammatory cells were also present adherent to the endothelium in the distal segments. CONCLUSIONS: Distal vasomotor function reflects an influence from the nature of a proximal intervention. The effect of irradiation on downstream conduit arteries to increase the threshold of contractility and suppress endothelium-dependent relaxation may be related to the presence of inflammatory cells at both the upstream-instrumented site as well as the distal location.

Analysis of Variance↗