Delayed papillary muscle rupture after radiofrequency catheter ablation: A case report.

BACKGROUND: With an increased number of surgical procedures involving the mitral annular region, the risk of mitral valve prolapse (MVP) has also increased. Previous studies have reported that worsening of MVP occurred early after radiofrequency catheter ablation (RFCA) at papillary muscles in ventricular tachycardia (VT) patients with preoperative MVP. CASE SUMMARY: We report a case where MVP and papillary muscle rupture occurred 2 wk after RFCA in a papillary muscle originated VT patient without mitral valve regurgitation or prolapse before. The patient then underwent mitral valve replacement with no premature ventricular contraction or VT. During the surgery, a papillary muscle rupture was identified. Pathological examination showed necrosis of the papillary muscle. The patient recovered after mitral valve replacement. CONCLUSION: Too many ablation procedures and energy should be avoided.

Catheter ablation of premature ventricular contractions originating from periprosthetic aortic valve regions.

BACKGROUND: Little is known about the ablation outcomes of premature ventricular contractions (PVCs) that originate from the periprosthetic aortic valve (PPAV) regions of patients with aortic valve replacement (AVR). METHODS AND RESULTS: Our study had 11 patients who underwent catheter ablation for PVCs arising from the PPAV regions (bioprosthetic aortic valve, n = 5; mechanical aortic valve, n = 6). The PVC characteristics, procedure characteristics, and efficacy of ablation were compared with the control group (n = 33). At baseline, the PPAV group had a lower left ventricular ejection fraction (mean [SD], 41% [12%] vs. 51% [8%]; p = .002). The rate of acute ablation success was 90.9% in the PPAV group. Ablation sites were identified above the left coronary cusp (LCC) and right coronary cusp commissure (LRCC) in one PVC, below the prosthetic valve in eight PVCs (four below LCC and four below LRCC), and within the distal coronary sinus in two PVCs. The mean procedure time, fluoroscopy time, and radiation in the PPAV group were all significantly greater than those in the control group (all p < .05). However, the number of radiofrequency ablation energy deliveries was not different. The PPAV group had a long-term success rate compared with the control group (72.7% vs. 87.9%, p = .48) and an increase of left ventricular ejection fraction from 43% to 49% after successful PVC ablation at follow-up (p < .001). Echocardiography showed no significant change in valve regurgitation after ablation. No new atrioventricular block occurred. CONCLUSION: PVCs arising from PPAV regions can be successfully ablated in patients with prior AVR, without damaging the prosthetic aortic valve and atrioventricular conduction.

Distinct origins and functions of cardiac orthotopic macrophages.

Macrophages are one cell type in the innate immune system. Recent studies involving macrophages have overturned the conventional concept that circulating bone marrow-derived blood mononuclear cells in the adult body continuously replace macrophages residing in the tissues. Investigations using refined technologies have suggested that embryonic hematopoiesis can result in the differentiation into macrophage subgroups in some tissues. In adulthood, these macrophages are self-sustaining via in situ proliferation, with little contribution of circulating bone marrow-derived blood mononuclear cells. Macrophages are integral component of the heart, accounting for 8% of the non-cardiac cells. The use of innovative molecular techniques in paradigm shifting researches has revealed the complexity of cardiac macrophages, including their heterogeneity and ontological diversity. Resident cardiac macrophages modulate the physiological and pathophysiological processes of the cardiovascular system, with distinct and crucial roles in healthy and injured hearts. Their functions include sensing of pathogens, antigen presentation, digesting cell debris, regulating inflammatory responses, generating distinct cytokines, and secreting some regulatory factors. More recent studies have revealed further functions of cardiac macrophages. This review focuses on macrophages within the cardiovascular system. We discuss evidence that has changed our collective view of cardiac macrophage subgroups, and improved our understanding of the different phenotypes, cell surface markers, heterogeneities, origins, developments, and the dynamic and separate roles of these cardiac macrophage subgroups in the steady state and injured hearts. This review may provide novel insights concerning the pathophysiology of cardiac-resident macrophages in cardiovascular diseases and innovative therapeutic strategies that could include the modulation of the role of macrophages in cardiovascular injuries.

Takotsubo cardiomyopathy associated with bronchoscopic operation: A case report.

BACKGROUND: Takotsubo cardiomyopathy (TTC), a syndrome of acute left ventricular (LV) dysfunction, is characterized by transitory hypokinesis of LV apices with compensatory hyperkinesis of the LV basal region. The symptoms of TTC mimic acute myocardial infarction, without significant coronary stenoses on coronary angiography. Echocardiogram plays a key role in the diagnosis and prognosis of TTC. New indicators from echocardiograms may be helpful in disease evaluation. CASE SUMMARY: A 67-year-old man with a 10-year history of non-small cell lung cancer was admitted to our hospital for emerging facial edema and dry cough. Bronchoscopic lavage, brushing, and biopsy were performed to evaluate tumor progression. During this procedure, he complained of left chest pain, nausea, and vomiting, with elevated troponin levels. Electrocardiogram showed sinus bradycardia with ST-segment elevation in I, AVL, and V4 to V6 leads. Coronary angiography revealed mild stenosis in the right coronary artery. Echocardiography showed hypokinesis of LV apices with compensatory hyperkinesis of the LV basal region. At the 7-d follow-up, echocardiographic pressure-strain analysis showed a normal LV ejection fraction, but partial recovery of LV myocardial work, which fully recovered 5 mo later. CONCLUSION: This is a case of TTC caused by bronchoscopic operation. We strongly recommend noninvasive myocardial work measured by echocardiographic pressure-strain analysis as a necessary supplementary test for the long-term follow-up of TTC.

α-adrenoceptor-mediated enhanced inducibility of atrial fibrillation in a canine system inflammation model.

The exact mechanism associated with inflammation and atrial fibrillation (AF) remains unknown. The aim of the present study was to investigate the roles of connexin 43 (Cx43) and a1­adrenergic receptor (α1­AR) activation in the pathogenesis of system inflammation­induced AF. A canine model of chronic low­grade system inflammation was established by administrating a low dose of lipopolysaccharide (LPS; 0.1 µg/kg) for 2 weeks. Programmed stimulation was applied on the right atrial appendage to determine the effective refractory periods (ERP) and the window of vulnerability (WOV). Tumor necrosis factor α (TNF­α) and interleukin 6 (IL­6) levels in plasma and atrial tissue were measured by ELISA. Cx43, Toll­like receptor 4 (TLR4) and nuclear factor κB (NF­κB) proteins were analyzed using western blotting or immunohistochemistry. Administration of LPS for 2 weeks increased the concentration of TNF­α and IL­6 in the plasma and right atrium. ERP was markedly shortened and cumulative WOV was significantly widened in the LPS group. Following treatment with LPS, the amount of Cx43 protein in the area of intercalated disk increased. In addition, a high­density of Cx43 in the lateral connection was identified. LPS also induced the activation of NF­κB in the canine atrium. Administration with the α1­AR blocker doxazosin prevented the production of LPS­induced inflammatory cytokine and reversed the enhanced vulnerability to atrial fibrillation. Doxazosin inhibited the LPS­induced increase in Cx43 protein and heterogeneous distribution, and prevented the activation of NF­κB. These results indicated that chronic low­grade system inflammation may increase the inducibility of AF in a canine model. The underlying mechanism may be involved in the LPS­induced activation of NF­κB, and the increase in Cx43 expression and lateral distribution via an α1-AR-dependent pathway.

Nerve growth factor rescues diabetic mice heart after ischemia/reperfusion injury via up-regulation of the TRPV1 receptor.

AIMS: Nerve growth factor (NGF), a member of the neurotrophin family, plays an essential role in diabetic neuropathy and ischemic heart disease. In the present study, we explored the potential role of NGF and the involvement of TRPV1 receptor in isolated diabetic mouse hearts following ischemia/reperfusion (I/R) injury. METHODS: Adenovirus-mediated NGF gene delivery was performed on diabetic and sham hearts 8weeks after streptozotocin treatment. The sciatic nerve conduction velocity was recorded using a biological signal acquisition system. Forty-eight hours after heart surgery, mice were subjected to I/R injury using a Langendorff system. Several cardiac parameters and the expression of associated molecules were analyzed during the experiment. RESULTS: The sciatic nerve conduction velocity was reduced in diabetic mice compared with that in control mice. Decreased expression of NGF, TRPV1, and the downstream neurotransmitters CGRP and SP was observed in the diabetic hearts. Adenovirus-mediated NGF overexpression reversed the reduction in TRPV1 and downstream neuropeptides, resulting in improved cardiac recovery post-I/R injury in diabetic hearts. The protective effect of NGF was abolished by CGRP8-37 (a selective CGRP antagonist), while it was preserved by low-dose capsaicin. CONCLUSIONS: The NGF-induced up-regulation of TRPV1 via the increased synthesis and release of endogenous CGRP leads to improved cardiac performance in I/R-injured diabetic heart.

Up-regulation of calcitonin gene-related peptide protects streptozotocin-induced diabetic hearts from ischemia/reperfusion injury.

BACKGROUND: Diabetic hearts are vulnerable to ischemia/reperfusion (I/R) injury. Pretreatment with exogenous calcitonin gene-related peptide (CGRP) exerts a cardioprotective effect against myocardial I/R injury. Our previous study found that the CGRP level was decreased in diabetic hearts. This study aimed to investigate whether up-regulation of CGRP could reduce I/R injury in diabetic hearts. METHODS AND RESULTS: Adenovirus encoding the CGRP gene (Ad-CGRP) was injected intramyocardially in mice with or without streptozotocin (STZ) treatment. Three days after injection, the hearts were subjected to in vivo and in vitro I/R. Myocardial infarct size, cardiac function, lactate dehydrogenase (LDH) level in plasma and effluents, and cell mitochondrial function were measured. After ischemia (30 min) and reperfusion (24h) in vivo, diabetes mellitus (DM) mice had greater myocardial infarct size than their nondiabetic counterparts, and released more LDH in plasma. However, CGRP gene transfer reduced myocardial infarct size and plasma LDH level in both non-DM and DM hearts. After 30 min global ischemia and 40 min reperfusion in vitro, the DM hearts demonstrated increased left ventricular end-diastolic pressure (LVEDP) and effluent LDH level, and decreased left ventricular developed pressure (LVDP), coronary flow (CF), as well as cell mitochondrial function, when compared with the non-DM hearts. Again, CGRP gene transfer could protect against I/R injury in both non-DM and DM hearts. CONCLUSIONS: Adenovirus-mediated up-regulation of CGRP gene expression protects diabetic hearts against I/R injury.

[Construction of recombinant adenovirus vector of calcitonin gene-related peptide gene and transfection to neonatal rat cardiomyocytes].

OBJECTIVE: To construct a recombinant adenovirus vector of calcitonin gene-related peptide (CGRP) by AdEasy system and to validate its expression in myocardial cells. METHODS: The full-length of CGRP gene cDNA was acquired by RT-PCR and cloned into pShuttle-CMV. After linearization with Pme I, the recombinant plasmid (pShuttle-CMV-CGRP) was transformed into E.coli BJ5183 by electroporation to construct the recombinant adenovirus plasmid AdEasy-pShuttle-CGRP. The recombinant adenovirus plasmids were transformed into E.coli XL10-Gold cells to be amplified. Then the recombinant plasmid was digested with Pac I and transfected to 293 cells to package recombinant adenovirus particles. PCR technique was used to detect target gene. The recombinant adenovirus particles were purified by CsC1 density gradient. The purified recombinant adenovirus was transfected to neonatal rat cardiomyocytes,and the recombinant adenovirus production was observed by fluorescent microscope. Expression of CGRP in hearts 7 days after intravenous delivery of adenoviral vectors AV-CGRP was determined by radioimmunoassay. RESULT: The RT-PCR products confirmed a full-length cDNA of CGRP gene in PUC(57) by sequencing. The corresponding double endonuclease and PCR analysis certified the successful cloning of the gene into the pShuttle-CMV. The recombinant adenovirus plasmid AdEasy-pShuttle-CGRP was digested by Pac I endonuclease to form the typical DNA segments, whose length was about 3 kb and 30 kb. PCR analysis and fluorescent microscope observation confirmed that the CGRP gene was inserted into the adenovirus vector with very strong power of transfection. The recombinant adenovirus particles infected neonatal rat cardiomyocytes successfully. Radioimmunoassay showed that delivery of AV-CGRP significantly increased the expression of CGRP in mice hearts. CONCLUSION: The recombinant adenovirus vector of CGRP gene has been constructed,and it can infect neonatal rat cardiomyocytes successfully. Somatic delivery of CGRP gene can significantly increase the expression of CGRP in mice hearts. The results may provide a sound foundation for further study on the value of CGRP as the target for gene therapy in both laboratory and clinical trials.

Cyclophosphamide protects against myocardial ischemia/reperfusion injury in rats: one of the therapeutic targets is high sensitivity C-reactive protein.

OBJECTIVE: Cyclophosphamide has a role of decreasing high-sensitivity C-reactive protein in the treatment of autoimmune disorders. The effect of cyclophosphasmide on high-sensitivity C-reactive protein was investigated in myocardial ischemia/reperfusion rat. METHODS: Open-chest rats were submitted to 30 minutes of ischemia and followed for 3, 12, or 24 hours of reperfusion. All 72 rats survived and were divided into sham, ischemia/reperfusion (I/R) and cyclophosphamide groups, and each group included 3 time-point subgroups (3, 12, and 24 hours; n = 8 for each subgroup). Cyclophosphamide (0.75 g/m(2)) or saline was intraperitoneally administrated in the cyclophosphamide or I/R group. A polyethylene tube was inserted into the left ventricular cavity to detect left ventricular systolic pressure, left ventricular end-diastolic pressure, and maximum rate of rise or fall of left ventricular pressure. In the end, blood was collected for detection of high-sensitivity C-reactive protein, and hearts were harvested for histopathologic assessment and infarct size determination. RESULTS: Compared with the I/R group, rats treated with cyclophosphamide showed a significant recovery in myocardial function with improved left ventricular systolic pressure (88.27 +/- 3.78 vs 68.62 +/- 3.78 mm Hg at 3 hours, 92.04 +/- 3.77 vs 63.74 +/- 4.87 mm Hg at 12 hours, and 90.41 +/- 3.98 vs 64.21 +/- 4.88 mm Hg at 24 hours; P < .05, respectively). Left ventricular end-diastolic pressure and maximum rate of rise or fall of left ventricular pressure also had similar trends. Infarct size was reduced (26.1% +/- 0.4% vs 40.4% +/- 0.4% at 3 hours, 21.6% +/- 0.4% vs 49.9% +/- 0.4% at 12 hours, and 21.6% +/- 0.4% vs 40.0% +/- 0.4% at 24 hours; P < .01, respectively). Histopathologic damage score was attenuated (1.83 +/- 0.14 vs 2.17 +/- 0.14 at 3 hours, 2.33 +/- 0.14 vs 3.17 +/- 0.14 at 12 hours, and 2.83 +/- 0.14 vs 3.83 +/- 0.14 at 24 hours; P < .01, respectively). Plasma high-sensitivity C-reactive protein concentration was significantly reduced (29.28 +/- 0.51 vs 32.26 +/- 0.51 ng/mL at 3 hours, 29.06 +/- 0.50 vs 31.8 +/- 0.51 ng/mL at 12 hours, and 28.61 +/- 0.51 vs 31.86 +/- 0.51 ng/mL at 24 h; P < .01, respectively). CONCLUSION: Cyclophosphamide protects myocardial ischemia/reperfusion injury in the rat with a decrease in plasma concentration of high-sensitivity C-reactive protein.

Effects of atorvastatin on calcium-regulating proteins: a possible mechanism to repair cardiac dysfunction in spontaneously hypertensive rats.

Previous clinical and experimental studies have demonstrated that statins, the inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, can improve left ventricular function in damaged hearts. Also, the normal expression of Ca(2+) regulatory proteins is critical for efficient myocardial function. However, it is still unclear whether the beneficial effect of statins on cardiac function is associated with alterations of Ca(2+) regulatory proteins. In this study, we investigated the effect of atorvastatin on cardiac function in spontaneously hypertensive rats (SHRs), focusing in particular on its impact on the expression of sarcoplasmic reticulum Ca(2+)-adenosine triphosphatase (SERCA2a), phospholamban (PLB) and its phosphorylated form (phosphorylated PLB), all of which are Ca(2+) regulatory proteins in myocardium. SHRs showed decreases in gene expression of SERCA2a and phosphorylated PLB, and reduction in SERCA activity in the left ventricular myocardium, as well as reduced cardiac function, compared to age-matched Wistar Kyoto rats (WKYs). Furthermore, we showed that in SHRs atorvastatin preserved cardiac dysfunction accompanied by positive alterations in calcium regulatory proteins, with up-regulation in expression of SERCA2a and phosphorylated PLB, and with improvement of SERCA activity. Thus, atorvastatin has positive effects on calcium regulatory proteins, which may be one of the mechanisms of the beneficial effect of statins on cardiac function in spontaneously hypertensive rats.

A novel splice mutation of HERG in a Chinese family with long QT syndrome.

Congenital long QT syndrome (LQTS) is a genetically heterogeneous disease in which six ion-channel genes have been identified. The phenotype-genotype relationships of the HERG (human ether-a-go-go-related gene) mutations are not fully understood. The objective of this study is to identify the underlying genetic basis of a Chinese family with LQTS and to characterize the clinical manifestations properties of the mutation. Single strand conformation polymorphism (SSCP) analyses were conducted on DNA fragments amplified by polymerase chain reaction from five LQT-related genes. Aberrant conformers were analyzed by DNA sequencing. A novel splice mutation in C-terminus of HERG was identified in this Chinese LQTS family, leading to the deletion of 11-bp at the acceptor splice site of Exon9 [Exon9 IVS del (-12-->-2)]. The mutation might affect, through deficient splicing, the putative cyclic nucleotide binding domain (CNBD) of the HERG K(+) channel. This mutation resulted in a mildly affected phenotype. Only the proband had a history of syncopes, while the other three individuals with long QT interval had no symptoms. Two other mutation carriers displayed normal phenotype. No sudden death occurred in the family. The 4 affected individuals and the two silent mutation carriers were all heterozygous for the mutation. It is the first splice mutation of HERG reported in Chinese LQTS families. Clinical data suggest that the CNBD mutation may be less malignant than mutations occurring in the pore region and be partially dominant over wild-type function.

[Profile on circadian blood pressure and the influencing factors in essential hypertensive patients after treatment].

OBJECTIVE: To explore the circadian blood pressure (BP) profile and its influencing factors in essential hypertensive patients after treatment. METHODS: Cross-sectional surveillance was carried out in essential hypertensive subjects after treatment whose clinic blood pressure had been under control as 140/90 mm Hg (1 mm Hg = 0.133 kPa) for at least one month. All patients underwent a twenty-four-hour ambulatory blood pressure monitoring device (spacelabs 90207). The nocturnal fall of blood pressure (BP) was calculated from (daytime mean BP-night-time mean BP)/daytime BP, while 'daytime' values were recorded between 6 h and 22 h and 'night-time' values between 22 h and 6 h. Non-dippers were defined as those whose nocturnal decrease in mean systolic BP and/or mean diastolic BP was < 10% of the daytime BP. Binary logistic regression analysis was used to evaluate the correlation between circadian blood pressure profile and factors as gender, age, height, body mass index (BMI), family history of premature cardiovascular disease, women under age 65 or men under age 55, smoking habits, grade of hypertension, and strategy of antihypertensive drugs. RESULTS: 208 treated essential hypertensive patients were enrolled in the study. 79 individuals were dippers and 129 were non-dippers. Data from logistic regression analysis showed that four factors as age, premature family history of cardiovascular disease, overweight or obesity, and strategy of antihypertensive drugs were significantly influencing the circadian blood pressure profile in treated hypertensive patients. The incidence of non-dippers in patients of 70 years of age or older and those between 60 and 69 were 3.3 and 2.3 times of those with less than 60 (P = 0.009 and 0.031, respectively). The prevalence of non-dippers in patients with a premature family history of cardiovascular disease was 3.7 times greater than those in subjects without a premature history of cardiovascular disease (P = 0.029). Similarly, the incidence of non-dippers in patients of overweight (24 /= 28) were 3.0 and 4.8 times of those in subjects of normal weight (P = 0.003 and 0.009, respectively). Compared with patients treated with long-acting calcium channel blockers (CCBs), patients treated with angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) alone had less prevalence of nondippers (OR = 0.139, P = 0.010). Patients treated with joint antihypertensive scheme including ACE inhibitors or ARBs(but not including diuretics) had the tendency of lower incidence of abnormal circadian blood pressure rhythm (OR = 0.453, P = 0.118). Patients treated with joint antihypertensive scheme including diuretics (not including ACE inhibitors or ARBs) and with joint antihypertensive strategy including diuretics and ACE inhibitors or ARBs had lower incidence of nondippers (OR = 0.378 and 0.273, respectively; P = 0.030 and 0.011, respectively). CONCLUSIONS: Approximately 2/3 treated essential hypertensive patients had a non-dipper blood pressure profile. Age, premature family history of cardiovascular disease, overweight/obesity, and antihypertensive drugs strategy were correlated with circadian blood pressure profile. Compared with long-acting CCBs, diuretics, ACE inhibitors or ARBs might be helpful in keeping the circadian blood pressure rhythm at normal range.

[Identification of a novel mutation at the point of low density lipoprotein receptor gene from a subject with familial hypercholesterolemia].

Family hypercholesterolemia (FH) is a genetic disorder caused by mutation in the low density lipoprotein receptor (LDLR) gene. It is characterized by a high concentration of low density lipoprotein (LDL), which frequently gives rise to tendon xanthenes and premature coronary artery disease. We studied a FH family ,which was diagnosed by clinical features and blood lipid tests. The Total cholesterol level of the family was 19.05 mmol/L and the LDL level was 17.06 mmol/L in the proband homozygous FH subjects, while the total cholesterol was 7.96 mmol/L and LDL was 5.55 mmol/L in the heterozygous FH subjects. DNA segments amplified with PCR were sequenced in heterozygous and homozygous FH patients. Two novel identical mutation alleles of GAG683GCG, which caused an amino acid change from Glu to Ala, were detected in Exon4 of LDL receptor gene in homozygous proband. DNA sequencing revealed that the proband's parents were heterozygotes with the same mutational alleles as the proband. These results are in coincidence with the clinical diagnoses. Moreover Epstein-Barr virus transformed lymphocytes (EBV-Ls) were derived by routine virus infection transforming protocol. The cells bounded with the fluorescently conjugated LDL were measured by fluorescence flow cytometry. The ratios of functional LDLR in EBV-Ls originated from homozygous FH, heterozygous FH and normal control were 7.02%, 62.64% and 84.69%, respectively. As a result, the homozygous FH patient's LDLR had 8.29% and the heterozygous FH patient's LDLR had 73.96% of the activity of the control. It is apparent that LDL receptor activity of homozygous FH subject is significantly lower than normal control. The data from fluorescence flow cytometry analysis of EBV-Ls strongly support the clinical diagnoses and the results of DNA sequencing. In accordance with the updated version of UMD-LDLR, the mutant GAG683GCG in Exon4 of LDLR gene which we have identified is a novel mutation of the LDLR gene in human with hypercholesterolemia.

[Effect of radiofrequency ablation on endothelial function and platelet activation].

OBJECTIVE: To investigate the effect of radiofrequency catheter ablation on endothelial function and platelet activation. METHODS: With radioimmunoassay, enzyme linked immunosorbent assay, cell labeling with monoclonal antibody and flow cytometry technique, thirty-one consecutive patients were checked for levels of plasma endothelin (ET), von willebrand's factor (vWF) and expression of platelet alpha-granule membrane glucoprotein (CD(62P)), platelet lysosome membrane glucoprotein (CD(63)) before, immediately and 47 - 115 hours after radiofrequency catheter ablation. RESULTS: There was no significant difference in the levels of plasma ET and vWF before and after catheter ablation; The rate of CD(62P) and CD(63) expression rate on platelets was (4.75 +/- 2.32)% and (9.62 +/- 4.08)% before catheter ablation, and it significantly increased to (7.64 +/- 5.25)% (t = 3.05, P < 0.01) and (12.23 +/- 5.70)% (t = 2.10, P < 0.05) immediately after catheter ablation and then returned to baseline levels 47 - 115 hours after catheter ablation. There was a positive correlation between the change of CD(62P) expression and total energy dose of radiofrequency (r = 0.30, P < 0.05). CONCLUSIONS: Radiofrequency catheter ablation did not bring about significant damage to endothelium but can increase expression of platelet membrane CD(62P), CD(63) and promote platelet activation, total energy dose of radiofrequency is one of important influencing factor.