Conquer coronary artery perforation with magic hands.

Coronary artery perforation (CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

Noninvasive Stereotactic Radiotherapy for PADN in an Acute Canine Model of Pulmonary Arterial Hypertension.

This study assesses the feasibility, safety, and effectiveness of noninvasive stereotactic body radiotherapy (SBRT) as an approach for pulmonary artery denervation in canine models. SBRT with CyberKnife resulted in reduced mean pulmonary artery pressure, pulmonary capillary wedge pressure, and pulmonary vascular resistance, and insignificantly increased cardiac output. In comparison to the control group, serum norepinephrine levels at 1 month and 6 months were significantly lower in the CyberKnife group. Computed tomography, pulmonary angiography, and histology analysis revealed that SBRT was associated with minimal collateral damage.

Presence of Severe Stenosis in Most Culprit Lesions of Patients with ST-segment Elevation Myocardial Infarction.

BACKGROUND: Previous studies revealed that culprit vessels of ST-segment elevation myocardial infarction (STEMI) were often related to mild or moderate stenosis. However, recent studies suggested that severe stenosis was primarily found in culprit lesions. The objective of this study was to analyze the stenosis severity of culprit lesions in STEMI patients and to clarify the paradoxical results. METHODS: A total of 489 consecutive STEMI patients who underwent primary percutaneous coronary intervention were retrospectively studied from January 2012 to December 2014. The patients were divided into three groups based on stenosis severity using quantitative coronary analysis: Group A, 314 cases, stenosis ≥70%; Group B, 127 cases, stenosis 50-70%; and Group C, 48 cases, stenosis ≤50%. The clinical, demographic, and angiographic data of all groups were analyzed. RESULTS: Patients in Group A exhibited a significantly higher prevalence of history of angina pectoris (95.9% vs. 62.5%, P< 0.001), multivessel disease (73.2% vs. 54.2%, P = 0.007), and lower cardiac ejection fraction (53.3 ± 8.6 vs. 56.8 ± 8.4, P= 0.009) than those in Group C. Multivariable analysis revealed that history of angina pectoris (odds ratio [OR]: 13.89, 95% confidence interval [CI]: 6.21-31.11) and multivessel disease (OR: 2.32, 95% CI: 1.25-4.31) were correlated with severe stenosis of the culprit lesion in Group A. CONCLUSIONS: Most culprit lesions in STEMI patients were severe stenosis. These patients exhibited a higher prevalence of angina history and multivessel diseases.

Anti-apoptotic effects of a calpain inhibitor on cardiomyocytes in a canine rapid atrial fibrillation model.

PURPOSE: This study was designed to evaluate the effects of a calpain inhibitor on cardiac muscle apoptosis in rapid pacing canine atrial fibrillation (AF) models. METHODS: Twenty one dogs were divided into three groups: a sham operation group, a control AF group and a calpain inhibitor group. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute. N-Acetyl-Leu-Leu-Met (1.0 mg/kg/day) was administered in the calpain inhibitor group for three weeks. The activity of calpain I and cardiomyocyte apoptosis were measured by fluorometry and TUNEL assay, respectively. Protein expression of caspase-3 was detected by Western blot. The localizations of caspase-3, caspase-8, bcl-2 and ARC were assessed by immunohistochemistry. RESULTS: In comparison to the sham operation group, the activity of calpain I was significantly increased in the control AF group (2.3 fold, p < 0.001), and decreased in the calpain inhibitor group (1.1 fold, p < 0.005). The calpain activity correlated with the apoptosis index (r = 0.9, p < 0.05). The apoptosis index was 1.0 +/- 0.2%, 11.8 +/- 6.8% and 3.5 +/- 2.1% in the sham operation group, control AF group and calpain inhibitor group, respectively. In the sham operation group, control AF group and calpain inhibitor group, the expressions of caspase-3 (13.0 +/- 1.9%, 52.8 +/- 4.3% and 33.6 +/- 3.7%), caspase-8 (40.1 +/- 5.3%, 92.6 +/- 6.5% and 55.3 +/- 5.9%), bcl-2 (65.8 +/- 6.1%, 52.0 +/- 5.7% and 69.9 +/- 5.3%) and ARC (70.2 +/- 8.6%, 68.8 +/- 7.3% and 81.5 +/- 8.8%) were calculated as immunohistochemical indexes, respectively. CONCLUSIONS: The calpain inhibitor N-Acetyl-Leu-Leu-Met attenuated apoptosis through a complicated network of apoptosis-related proteins, which may result in improvement of structural remodeling in atrial fibrillation.

Probucol attenuates atrial autonomic remodeling in a canine model of atrial fibrillation produced by prolonged atrial pacing.

BACKGROUND: We hypothesize that increased atrial oxidative stress and inflammation may play an important role in atrial nerve sprouting and heterogeneous sympathetic hyperinnervation during atrial fibrillation (AF). To test the hypothesis, we examined whether the antioxidant and anti-inflammatory treatment with probucol attenuates atrial autonomic remodeling in a canine model of AF produced by prolonged rapid right atrial pacing. METHODS: Twenty-one dogs were divided into a sham-operated group, a control group and a probucol group. Dogs in the control group and probucol group underwent right atrial pacing at 400 beats per minute for 6 weeks, and those in the probucol group received probucol 1 week before rapid atrial pacing until pacing stopped. After 6-week rapid atrial pacing, general properties including left atrial structure and function, atrial hemodynamics and the inducibility and duration of AF were measured in all the groups. Atrial oxidative stress markers and serum C-reactive protein (CRP) concentration were estimated. The degree of nerve sprouting and sympathetic innervation at the right atrial anterior wall (RAAW) and the left atrial anterior wall (LAAW) were quantified by immunohistochemistry, atrial norepinephrine contents were also detected. Atrial beta-nerve growth factor (beta-NGF) mRNA and protein expression at the RAAW and LAAW were assessed by real-time quantitative RT-PCR and Western blotting respectively. RESULTS: Atrial tachypacing induced significant nerve sprouting and heterogeneous sympathetic hyperinnervation, and the magnitude of nerve sprouting and hyperinnervation was higher in the RAAW than in the LAAW. Atrial beta-NGF mRNA and protein levels were significantly increased at the RAAW and LAAW, and the upregulation of beta-NGF expression was greater at the RAAW than at the LAAW in the control group. The beta-NGF protein level was positively correlated with the density of sympathetic nerves in all groups. Probucol decreased the increase of CRP concentration and attenuated atrial oxidative stress caused by atrial tachypacing. In addition, probucol could effectively inhibit atrial beta-NGF upregulation, significantly attenuate atrial nerve sprouting and heterogeneous sympathetic hyperinnervation, and dramatically reduce the inducibility and duration of AF. CONCLUSIONS: The atrial over-expression of beta-NGF possibly caused by increased oxidative stress and inflammation may be the main mechanism underlying atrial autonomic remodeling during AF. Probucol attenuates atrial autonomic remodeling possibly by its antioxidant and anti-inflammatory actions.

[Influence of oxidative stress on atrial myocardium pathohistological and ultrastructural changes in atrial fibrillation: experiment with dogs].

OBJECTIVE: To evaluate the effects of oxidative stress on the protein expression of atrial calpain I and pathohistological and ultrastructural changes of atrial myocardium in atrial fibrillation (AF). METHODS: Twenty dogs were all implanted with pacemaker in a subcutaneous pocket and attached to a screw-in epicardial lead in right atrial appendage. They were randomly divided into 3 groups: sham-operation group (n = 6 without pacing), control group (n = 7 per minutes for 6 weeks), and probucol group (n = 7, pacing 1 week after recovery for 6 weeks, and administration of probucol 100 mg x kg(-1) x d(-1) 1 week before pacing till the end of pacing). One thin silicon plaque containing 4 pairs of electrodes were sutured to the right atrium. The dogs in control group, probucol group were paced at 400 beats per minutes for 6 weeks. Then the dogs were killed with their hearts taken out. The expression of atrial calpain I was measured by Western-blotting and immunohistochemistry. The pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. The inducibility and duration of AF were measured in the control group and probucol group. The indexes of oxidative stress total anti-oxidation capability (T-AOC), malonyldiadehyde (MDA), and scavenging activities of superoxide anion (O2-) radical were measured by colorimetric method. RESULTS: The percentage of myolysis in the left and right atria of the control group were (53.6 +/- 11.8)% and. (58.5 +/- 9.2)% respectively, significantly higher than those of the sham operation group [(4.4 +/- 3.1)% and (4.1 +/- 2.9)% respectively, both P < 0.01]. The percentage of myolysis in the left and right atria of the probucol group were (12.3 +/- 3.2)% and (12.0 +/- 2.6)% respectively, both significantly lower than those of the control group (both P < 0.01). The protein expression of calpain I of the control group was significantly higher than that of the sham-operation group, and the protein expression of calpain I of the probucol group was significantly lower than that of the control group. The AF inducibility rate after pacing of the probucol group was 60%, significantly lower than that of the control group (92.9%, P < 0.01). The average AF duration time after pacing of the probucol group was (601 +/- 328) s, significantly shorter than that of the control group (1458 +/- 498) s. The indexes of oxidative stress in probucol group were lower than the level in control group. The MDA levels of the probucol group was (3.08 +/- 0.20) mmol/mg protein, significantly lower than that of the control group (4.15 +/- 0.23) mmol/mg protein). The anti-O2- and T-AOC level of the probucol group were 279 +/- 20 U/g protein and 30.5 +/- 1.3 nmol/mg protein, both significantly higher than those of the control group (215 +/- 16 U/g protein and 25.6 +/- 1.5 nmol/mg protein respectively, both P < 0.01). There were more sarcomere vacuolization and dissolution in atrial myocytes in the control group than in the sham operation group. And the pathohistological and ultrastructural changes of the probucol were lighter than those of the control group. CONCLUSION: Probucol prevents the pathohistological and ultrastructural changes in atrial myocardium by inhibiting calpain I expression, thus suppressing atrial structural remodeling, and preventing the induction and promotion of AF.

Calpain I inhibition prevents atrial structural remodeling in a canine model with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is accompanied by atrial structural remodeling. Calpain activity is induced during AF. To test a causal relationship between calpain activation and atrial structural changes, N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, was utilized in a canine AF model. METHODS: Fifteen dogs were randomly divided into 3 groups: sham-operated group, control group and calpain inhibitor group; each with 5 dogs. Sustained AF was induced by rapid right atrium pacing at 600 beats per minute for 3 weeks. ALLM was administered at a dosage of 1.0 mg x kg(-1) x d(-1) in the calpain inhibitor group. Three weeks later, the proteolysis, protein expression of TnT and myosin, calpain I localization and expression and structural changes were examined in left atrial free walls, right atrial free walls and the interatrial septum respectively. Atrial size and contractile function were also measured by echocardiography. RESULTS: Long-term rapid atrial pacing induced marked structural changes such as enlarged atrial volume, myolysis, degradation of TnT and myosin, accumulation of glycogen and changes in mitochondrial shape and size, which were paralleled by an increase in calpain activity. The positive correlation between calpain activity and the degree of myolysis (r(s) = 0.90 961, P < 0.0001) was demonstrated. In addition to structural abnormalities, pacing-induced atrial contractile dysfunction was observed in this study. The pacing-induced atrial structural alterations and loss of contractility were partially prevented by the calpain inhibitor ALLM. CONCLUSIONS: Activation of calpain represents key features in the progression towards overt structural remodeling. Calpain inhibitor, ALLM, suppressed the increased calpain activity and reversed structural remodeling caused by sustained atrial fibrillation in the present model. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.

[Effect of calpain 1 on structural remodeling and contractile dysfunction in atrial fibrillation: experiment with dogs].

OBJECTIVE: To test the causal relationship between calpain activation and atrial structural changes during atrial fibrillation (AF). METHODS: The tip of a spiral mono-polar pacing lead was fixed to the right atrial appendages of 15 dogs randomly divided into 3 equal groups: calpain inhibitor group, undergoing continuous pacing with the impulse of 600 beats/min for 3 weeks and intravenous injection of N-acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor for 3 weeks; control group, undergoing continuous pacing and intravenous injection of dimethyl sulfoxide (DMSO; and sham operation group, given DMSO injection without pacing. Ultrasonography was used to observe the changes of the structures of left atrium and left atrial appendage and the heart function as well. Specimens of atrial muscles were obtained. Calpain 1 activity was detected by Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin method. HE staining was conducted to observe the myolysis. Western blotting was used to detect the protein expression of troponin I (TnI) and myosin. RESULTS: The left atrial ejection fraction (LAEF) of the ALLM group was (41 +/- 6)%, significantly higher than that of the control group [(34 +/- 9)%, P < 0.05]. The left atrial appendage ejection fraction (LAAEF) of the ALLM group was (41 +/- 6)%, significantly higher than that of the control group [(35 +/- 6)%, P < 0.05]. Myolysis was extensive in the control group [(71.5 +/- 10.2)%], relatively rare in the ALLM group [(12.3 +/- 16.5)%], and was not seen in the sham operation group, with significantly differences among the 3 groups (all P < 0.01). The calpain 1 activity was positively correlated with the degree of myolysis (r(s) = 0.90 961, P < 0.01). The TnI level of the control group was (43 +/- 12)% that of the sham operation group (P = 0.001), the TnI level of the ALLM group was (51 +/- 11)% that of the sham operation group (P = 0.002) and was significant higher than that of the control group (P = 0.01). The level of myosin of the control group was (51 +/- 11)% that of the sham operation group (P = 0.002), and that of the ALLM group was (149 +/- 33)% that of the control group (P = 0.005). CONCLUSION: Activation of and upregulation of expression of calpain participate in the structural remodeling of left atrial cardiac muscle and contractile dysfunction. Calpain inhibitor suppresses the increased calpain activity and reverses the structural remodeling of sustained atrial fibrillation. Calpain inhibition may therefore provide a possibility for therapeutic intervention in AF.

[Calpain I inhibition prevents pacing-induced structural remodeling for atrial fibrillation in canine].

OBJECTIVE: To study the relation of the structural remodeling processes and activation of calpain I. METHODS: Fifteen dogs were randomly divided into three groups. The dogs in pacing group (n=5) and inhibitor group (n=5) were subjected to 3 weeks of rapid atrial pacing at 600 beats/min, control dogs (n=5) were in sham-operated group. The dogs in inhibitor group were administered intravenous N-Acetyl-Leu-Leu-Met (ALLM), a calpain inhibitor, and in pacing group and sham-operated group were administered intravenous DMSO. The activity of calpain I was measured by hydrolyzing Suc-Leu-Leu-Val-Tyr-7-amino-4-methyl-coumarin. The ultrastructure of atrium was examined by light and electron microscopy. TnT expression was assessed by Western blot. Echocardiography examination was performed in all the three groups. RESULTS: Calpain I activity was significantly increased in pacing group (2.3-fold, P<0.01), and decreased in inhibitor group (1.1-fold, P>0.05), compared to sham-operated group respectively. The percentages of myolysis were (76.7 +/- 5.9)% and (20.8 +/- 8.1)% in pacing group and inhibitor group respectively (P<0.01). TnT expression decreased in the rapid pacing-induced persistent atrial fibrillation, and these effects were inhibited by calpain I inhibitor ALLM. The area and volume of left atrium tended to increase after 3 weeks ALLM treatment in inhibitor group, but the change was not as prominent as in pacing group (P<0.05). CONCLUSIONS: ALLM can decrease calpain I activity, and prevent canine atrial cardiomyocyte structural remodeling during atrial fibrillation. This study provided a capacity of atrial cardiomyocyte protection.

The effects of cilazapril and valsartan on the mRNA and protein expressions of atrial calpains and atrial structural remodeling in atrial fibrillation dogs.

Owing to relative inefficacy and side effects of currently available antiarrhythmic drugs, current interest has shifted to treatments that target atrial fibrillation (AF) substrate. It has been suggested that calpain-induced atrial structural remodelling is under the control of renin-angiotensin system during AF. The purpose of this study is to investigate the effects of cilazapril and valsartan on the mRNA and protein expression of atrial calpains and atrial structural remodelling in AF dogs induced by chronic rapid atrial pacing. Twenty-seven dogs were randomly divided into sham-operated group (n = 6), control group (n = 7), cilazapril group (n = 7) and valsartan group (n = 7). One thin silicon plaque containing 4 pairs of electrodes was sutured to each atrium. A pacemaker was implanted in a subcutaneous pocket and attached to a screw-in epicardial lead in the right atrial appendage. The dogs in control group, cilazapril group and valsartan group were paced at 400 beats per minutes for 6 weeks. The dogs in cilazapril and valsartan groups received cilazapril (1mg x kg(-1)x d(-1)) or valsartan (30mg x kg(-1) x d(-1)) 1 week before rapid atrial pacing until pacing stop respectively. Transthoracic and transoesophageal echocardiographic examinations were performed in order to detect the changes of left atrium volume and contractile function. The inducibility and duration of AF were measured in all the groups. The expressions of atrial calpain I and calpain II mRNA were semi-quantified by reverse transcription-polymerase chain reaction. The protein levels of calpain I and calpain II in atrial myocardium were measured by Western-blot method. Pathohistological and ultrastructural changes in atrial tissue were tested by light and electron microscopy. Compared with the sham-operated control group, dramatic smaller left atrium and left atrial appendage volumes and significant higher atrial contractile function were observed in the cilazapril and valsartan groups. After 6-week atrial tachy-pacing, the mRNA and protein expressions of calpain I increased dramatically in the control group than that in the sham group, tissue calpain protein expression in all groups significantly correlated with the myolysis (r = 0.89, P < 0.01). Cilazapril and valsartan could significantly inhibit the gene and protein expressions of calpain I. No differences were found in the expression of calpain II mRNA and protein between the groups. Compared with atrial myocytes obtained from sham dogs, atrial myocytes from the control group dogs showed a reduced number of sarcomeres, a significant higher myolytic area of atria (24.3% vs. 3.1%, P < 0.01), increased vacuolization and dissolution. Cilazapril and valsartan could effectively prevent the pathohistological and ultrastructural changes induced by chronic rapid atrial pacing, dramatically decrease the area of myolysis (P < 0.05) and significantly reduce the inducibility and duration of AF. The expression of calpain I mRNA and protein increased remarkably in AF dogs. Cilazapril and valsartan can inhibit calpain I up-regulation, suppress atrial structural remodeling, and prevent the induction and promotion of AF in chronic rapid atrial pacing dogs.