Enterococcus faecalis Extracellular Vesicles Promote Apical Periodontitis.

Enterococcus faecalis is an important contributor to the persistence of chronic apical periodontitis. However, the mechanism by which E. faecalis infection in the root canals and dentinal tubules affects periapical tissue remains unclear. Bacterial extracellular vesicles (EVs) act as natural carriers of microbe-associated molecular patterns (MAMPs) and have recently attracted considerable attention. In this study, we investigated the role of EVs derived from E. faecalis in the pathogenesis of apical periodontitis. We observed that E. faecalis EVs can induce inflammatory bone destruction in the periapical areas of mice. Double-labeling immunofluorescence indicated that M1 macrophage infiltration was increased by E. faecalis EVs in apical lesions. Moreover, in vitro experiments demonstrated the internalization of E. faecalis EVs into macrophages. Macrophages tended to polarize toward the M1 profile after treatment with E. faecalis EVs. Pattern recognition receptors (PRRs) can recognize MAMPs of bacterial EVs and, in turn, trigger inflammatory responses. Thus, we performed further mechanistic exploration, which showed that E. faecalis EVs considerably increased the expression of NOD2, a cytoplasmic PRR, and that inhibition of NOD2 markedly reduced macrophage M1 polarization induced by E. faecalis EVs. RIPK2 ubiquitination is a major downstream of NOD2. We also observed increased RIPK2 ubiquitination in macrophages treated with E. faecalis EVs, and E. faecalis EV-induced macrophage M1 polarization was notably alleviated by the RIPK2 ubiquitination inhibitor. Our study revealed the potential for EVs to be considered a virulence factor of E. faecalis and found that E. faecalis EVs can promote macrophage M1 polarization via NOD2/RIPK2 signaling. To our knowledge, this is the first report to investigate apical periodontitis development from the perspective of bacterial vesicles and demonstrate the role and mechanism of E. faecalis EVs in macrophage polarization. This study expands our understanding of the pathogenic mechanism of E. faecalis and provides novel insights into the pathogenesis of apical periodontitis.

[Surgical treatment of primary liver cancer:a report of 10 966 cases].

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986－1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation (P>0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively (P=0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively(P<0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively(P=0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively (P<0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively (P=0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively(P=0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection(P=0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection(P=0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.

[A clinicopathological classification analysis of ocular mass lesions in 7 910 cases].

Objective: To investigate the anatomical region, histopathological classification and histogensis distribution of ocular mass lesions in South China. Methods: Retrospective cases study. The clinical and pathological data of 7 910 samples with ocular (adnexal) tumors or proliferative lesions which were examined from January 2000 to May 2018 were retrospectively retrieved. The constituent ratios of ocular mass lesions in different anatomical regions and histogenesis have been analyzed. Results: There were 3 445 males and 4 465 females aged from 3 months to 106 years. Classification by anatomical region. Eyelid 4 976 cases (62.9%): benign-pigmented nevus (31.7%, 1 342/4 235), squamous cell papilloma (12.3%, 519/4 235), seborrheic keratosis (9.4%, 396/4 235); malignant-basal cell carcinoma (48.5%, 359/741), sebaceous gland carcinoma (34.4%, 255/741), squamous cell carcinoma (12.3%, 91/741). Ocular surface 1 449 cases (18.3%): benign-pigmented nevus (26.6%, 359/1 348), squamous cell papilloma (12.8%, 173/1 348); malignant-lymphoma (34.7%, 35/101), squamous cell carcinoma (30.7%, 31/101).Orbit 1 485 cases (18.8%): benign-hemangioma (28.5%, 332/1 167), lacrimal gland (duct) cyst(13.2%, 154/1 167); malignant-lymphoma (44.7%, 142/318), adenoid cystic carcinoma (10.1%, 32/318). Classification by histogenesis: epithelial 2 145 cases (27.1%), cutaneous appendages 378 cases (4.8%), cystoid 1 068 cases (13.5%), mesenchymal 748 cases (9.5%), lymph-hematopoietic 225 cases (2.8%), neurogenic 31 cases (0.4%), melanocytic 1 765 cases (22.3%), others 1 550 cases (19.6%). Conclusions: Over the past 18 years, the ocular tumors identified at the Second Affiliated Hospital, Zhejiang University School of Medicine most frequently occur in eyelid and originate from epithelium. The most common types are as followings. Benign lesions: pigmented nevus, squamous cell papilloma are the most common types for eyelid and ocular surface, whereas hemangioma, lacrimal gland (duct) cyst and epidermoid cyst are the most common types for orbit. Malignant cancers: basal cell carcinoma is the most prevalent disease in eyelid, whereas lymphoma occurs more frequently in ocular surface and orbit. (Chin J Ophthalmol, 2019, 55: 847-853).

[Association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma: a meta-analysis].

Objective: To investigate the association between miR-146a single nucleotide polymorphism and genetic susceptibility to hepatocellular carcinoma (HCC). Methods: PubMed, Web of Science, Cochrane Library, Wanfang Data, and Google Scholar were searched for case-control studies on the association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC published up to October, 2016 in Chinese or English. The Q-statistics test was used to evaluate the heterogeneity of these articles. Results: A total of 18 articles with 5 610 cases and 7 531 controls were included for the meta-analysis. There was no significant association between miR-146a single nucleotide polymorphism and genetic susceptibility to HCC. The odds ratio (OR), 95% confidence interval (95% CI), and P values for the five genetic models were as follows: the allele model C/G (OR = 0.99, 95% CI 0.88-1.06, P = 0.440); the heterozygous model CG/GG (OR = 0.99, 95% CI 0.90-1.10, P = 0.898); the homozygous model CC/GG (OR = 0.91, 95% CI 0.75-1.10, P = 0.314); the dominant model CC+CG/GG (OR = 0.97, 95% CI 0.79-1.19, P = 0.759); the recessive model CG+GG/CC (OR = 1.05, 95% CI 0.94-1.18, P = 0.405). A subgroup analysis of race, source of control population, and Hardy-Weinberg equilibrium were performed in these five genetic models, and miR-146a single nucleotide polymorphism increased the susceptibility to HCC only in the control population-based subgroups of the recessive model CG+GG/CC (OR = 1.20, 95% CI 1.02-1.40, P = 0.024). There was no association between miR-146a rs2910164 polymorphism and susceptibility to HCC in all the other subgroups. A stratified analysis of HBV infection revealed that miR-146a rs2910164 polymorphism increased the risk of HBV-positive HCC (OR = 1.26, 95% CI 1.10-1.49, P = 0.001). Conclusion: There is no significant association between miR-146a rs2910164 polymorphism and the risk of HCC, but miR-146a rs2910164 polymorphism may increase the risk of HBV-positive HCC.

Contributions of polymorphisms in miR146a, miR196a, and miR499 to the development of hepatocellular carcinoma.

Hepatocellular carcinoma is one of the most common malignant tumors worldwide; it is estimated that there were 782,000 new cases in 2012. MicroRNAs (miRNAs) play an important role in carcinogenesis by regulating oncogenes and tumor suppressors. We investigated the role of miR-146a, miR-196a2, and miR-499 polymorphisms in the risk of hepatocellular carcinoma in a Chinese population. Hepatocellular carcinoma patients (175) and healthy controls (302) were recruited between April 2013 and March 2015. Genotype analysis of miR-146a, miR-196a2, and miR-499 polymorphisms was carried out by polymerase chain reaction-restriction fragment length polymorphism. There was a significant difference between the genotype distribution of miR-196a2 in hepatocellular carcinoma patients and controls (X2 = 17.23, P < 0.001). CG and GG miR-146a genotypes significantly elevated the risk of hepatocellular carcinoma compared with the CC genotype, with adjusted ORs (95%CI) of 3.05 (1.07-8.70) and 4.96 (1.64-14.97), respectively. In the recessive model, the CG + GG genotype had a 3.75-fold risk of hepatocellular carcinoma compared with the CC genotype, with an adjusted OR (95%CI) of 3.75 (1.39-10.11). However, no significant association was observed between miR-196a2 and miR-499 variants and risk of hepatocellular carcinoma in the co-dominant, dominant, and recessive models. The miR-146a polymorphism is a G to C substitution that causes a mismatch in the stem-loop of miRNA, which influences how the expression and transcriptional regulation of miRNA affects its target genes. Our study revealed that the GG and CG genotypes of miR-146a increased the risk of hepatocellular carcinoma in the Chinese population.

[Comparison between poly hydroxy acrylic acid and Van-clear replacing the traditional reagents to detect the cervical hTERC genes by adopting FISH technique].

OBJECTIVE: To observe the difference of the human telomeres RNA component (hTERC) genes' amplification in the cervical tissue by applying the environment-friendly fixative poly hydroxy acrylic acid and the transparent dewaxing solution Van-clear separately or jointly to replace the traditional fixative 4% (volume fraction) neutral buffered formalin and the conventional transparent dewaxing solution xylene in the use of fluorescence in situ hybridization (FISH) for detection. METHODS: In the study, 255 cases of cervical tissue specimens submitted by the Department of Gynecology in Zhongshan Boai Hosipital were collected from Mar. 2013 to Apr. 2015. Four samples were taken from the same lesion site. All the cases were divided into 4 groups and named group A, B, C, and D. Group A used 4% neutral buffered formalin fixed and xylene dewaxing to make slices. Group B used poly hydroxy acrylic fixed and xylene dewaxing to make slices. Group C used 4% neutral buffered formalin fixed and Van-clear transparent to make slices. Group D used poly hydroxy acrylic fixed and Van-clear transparent dewaxing to make slices. The amplification of hTERC genes in the four groups of cervical specimens was also detected by FISH technique. RESULTS: When the hTERC genes were detected by FISH method under the fluorescence microscope, it was obvious that the tissue profile and the background of group A, B, C and D were all clear. The probe was fixed in the accurate position so that the bright red or green fluorescence signals were easily found in these four groups. Compared with the positive rate of group A, there was no statistical significance in that of group B, C and D (P>0.05). At the same time, the coincidence rate of the FISH results was high, which showed that the new environment-friendly reagent had no significant difference in the detection of cervical hTERC genes by FISH technique. CONCLUSION: It is possible for the environment-friendly reagent poly hydroxy acrylic acid and Van-clear to replace 4% neutral buffered formalin and xylene separately or jointly to detect the cervical hTERC genes by adopting FISH technique.

Molecular cloning, sequence characterization of a novel pepper gene NADP-ICDH and its effect on cytoplasmic male sterility.

NADP-dependent isocitrate dehydrogenase (NADP-ICDH) is an important enzyme involved in energy metabolism. The complete coding sequence of the pepper (Capsicum annuum) NADP-ICDH gene was amplified using a reverse transcriptase PCR based on the conserved sequence information of the tomato and other Solanaceae plants and known highly homologous pepper ESTs. Nucleotide sequence analysis revealed that the pepper NADP-ICDH gene encodes a protein of 415 amino acids that has high homology with the proteins of seven species, Solanum tuberosum (100%), Citrus limon (98%), Daucus carota (98%), Nicotiana tabacum (98%), Vitis vinifera (99%), Arabidopsis thaliana (97%), and Oryza sativa (98%). Tissue expression analysis demonstrated that the pepper NADP-ICDH gene is over expressed in flower, pericarp and seed, moderately in placenta, weakly in stem and leaf, hardly expressed in root. At the abortion stages, activities and expression levels of NADP-ICDH in anthers of a sterile line were strongly reduced, while those in an F(1) hybrid remained normal. Activities and expression levels of NADP-ICDH were too low to maintain balanced energy metabolism in the sterile line, which indicated that stable transcripts of NADP-ICDH are necessary to maintain energy metabolism at a normal level. When the restorer gene was transferred to the cytoplasmic male sterile line, activities and expression level of NADP-ICDH were regulated by the restorer gene and became stable. The restorer gene likely plays an important role in keeping the balance of the energy metabolism within normal levels during microspore development.

Vg1 orthology in the direct developing frog, Syrrhophus cystignathoides campi.

Syrrhophus cystignathoides campi is a direct developing frog species that matures without passing through a larval (tadpole) stage. We have cloned and sequenced the Syrrhophus cDNA orthologous to the Xenopus Vg1 cDNA. The Syrrhophus Vg1 (sVg1) cDNA spans 1323 nucleotides and encodes a predicted protein of 345 amino acids which is 81% identical at its carboxyl terminal end to Xenopus Vg1. In addition, it contains seven conserved cysteine residues present in all Vg1 related proteins. Despite this high degree of similarity it is apparently missing a conserved N-linked glycosylation site and has an altered proteolytic processing sequence. Interestingly it is also missing a nine nucleotide sequence in its 3' UTR believed to be important for mRNA localization in Xenopus and Drosophila. These sequence variations could alter the functional expression and localization of the protein.

[Endoscopic injection sclerotherapy for esophageal varices: studies on methodology and complication].

From November 1985 to February 1991, sixty patients were randomized to three groups of intravariceal sclerotherapy: (1) many punctures of low quantity sclerosant, (2) one puncture of large quantity sclerosant, and (3) one puncture of large quantity sclerosant with transendoscopic balloon. The early effects and complications were investigated. Varices eradication was reached 91.2% in group 1, significantly higher than group 2 (58.3%) (P < 0.05), similar to group 3(89.9%). However, balloon group (group 3) required shorter duration than group 1 (12.6 vs. 21.7 days) (P < 0.05). There were no significant differences in complications, but all 6 esophageal stenosis were in group 1, recurrent bleeding was 11.4% in group 1.35.7% in group 2 and 0 in group 3 during sclerotherapy sessions. Further more, we found though attempted to inject into variceal veins, accurate intravariceal injection reached only 46.8% in accordance with venographic findings. We conclude that sclerotherapy with transendoscopic balloon seems to be more simple, safer, and required short time to produce successful variceal sclerosis.

Coronary vasodilator reserve in ischemic myocardium of the exercising dog.

BACKGROUND: Previous work has reported that coronary vasodilator reserve may persist in myocardium rendered ischemic by hypoperfusion. This study investigated the presence and extent of residual coronary vasomotor tone in myocardial regions made acutely ischemic by a flow-limiting coronary stenosis during exercise. METHODS AND RESULTS: Studies were done in chronically instrumented dogs undergoing treadmill exercise in the presence of a coronary stenosis that decreased distal left circumflex coronary artery perfusion pressure to approximately 40 mm Hg. Measurements of myocardial blood flow were made with radioactive microspheres during exercise (6.5 km/hr, 6% grade) before and during intracoronary infusion of the potent coronary vasodilator adenosine (40 micrograms/kg/min). Distal coronary perfusion pressure was held equal before and during intracoronary adenosine infusion (43 +/- 5 versus 42 +/- 5 mm Hg) by adjusting the hydraulic coronary occluder. During exercise in the presence of a coronary stenosis, myocardial blood flow (milliliter per minute per gram) was significantly reduced in all layers of the ischemic posterior region compared with the nonischemic anterior region. During intracoronary adenosine infusion, with no change in coronary perfusion pressure, myocardial blood flow was significantly increased compared with preadenosine flows for both the subendocardial layer flow (1.03 +/- 0.74 versus 0.66 +/- 0.50; p less than 0.05) and mean transmural flow (1.54 +/- 0.59 versus 1.16 +/- 0.36; p less than 0.05). In the presence of a coronary stenosis, regional myocardial segment shortening in the ischemic region during exercise fell significantly to 49 +/- 8% of shortening in the absence of a coronary stenosis but improved modestly during adenosine infusion (65 +/- 7 versus 49 +/- 8%; p less than 0.05). CONCLUSIONS: These results indicate that adenosine-responsive coronary vasodilator reserve persists during exercise-induced myocardial ischemia and suggest that residual microvascular vasoconstrictor tone may affect the extent of myocardial hypoperfusion occurring consequent to a flow-limiting coronary stenosis.

Oxygen consumption and coronary reactivity in postischemic myocardium.

Coronary vascular responses in regions of reversible postischemic myocardial contractile dysfunction (stunned myocardium) were examined in chronically instrumented, awake dogs. Left anterior descending coronary artery blood flow and oxygen extraction, aortic and left ventricular pressures, and regional myocardial segment shortening were determined. Regional myocardial blood flow was measured with microspheres. Coronary reactive hyperemia and vasodilator reserve, and regional myocardial oxygen consumption were determined. Three sequential 10-minute left anterior descending coronary artery occlusions separated by 30-minute reperfusion periods resulted in progressive postischemic dysfunction so that 1 hour after the final coronary artery occlusion, myocardial segment shortening was reduced to 37% of baseline. Despite this decrease in contractile function, left anterior descending artery flow (19.6 +/- 2.6 vs. 18.4 +/- 3.0 ml/min), myocardial blood flow and the transmural distribution of flow measured with microspheres, and regional myocardial oxygen consumption were unchanged. Although the coronary vasodilator reserve in response to adenosine was unaltered (63 +/- 9 vs. 70 +/- 15 ml/min), the reactive hyperemia response to a 10-second coronary occlusion was decreased in intensity (debt repayment ratio = 474 +/- 78% vs. 322 +/- 74%; p less than 0.05) and duration (57 +/- 9.1 vs. 35 +/- 4.5 seconds; p less than 0.05), while the peak flow response was unchanged (57 +/- 6.8 vs. 60 +/- 7.1 ml/min). Thus, in the intact awake animal postischemic myocardial contractile dysfunction was not associated with decreased myocardial oxygen consumption and did not impair the normal relation between coronary blood flow and myocardial oxygen utilization. Although coronary vessels showed a normal ability to vasodilate in response to adenosine, coronary reactive hyperemia was reduced.

Role of adenosine in coronary vasodilation during exercise.

This study examined the hypothesis that increases in myocardial blood flow during exercise are mediated by adenosine-induced coronary vasodilation. Active hyperemia associated with graded treadmill exercise and coronary reactive hyperemia were examined in chronically instrumented awake dogs during control conditions, after intracoronary infusion of adenosine deaminase (5 units/kg/min for 10 minutes), and after adenosine receptor blockade with 8-phenyltheophylline. Both adenosine deaminase and 8-phenyltheophylline caused a rightward shift of the dose-response curve to intracoronary adenosine; 8-phenyltheophylline was significantly more potent than adenosine deaminase. Adenosine deaminase caused a 33 +/- 7 to 39 +/- 3% decrease in reactive hyperemia blood flow following coronary occlusions of 5-20 seconds duration, respectively, while 8-phenyltheophylline produced a 40 +/- 6 to 62 +/- 8% decrease in reactive hyperemia. Increasing myocardial oxygen consumption during treadmill exercise was associated with progressive increase of coronary blood flow. Neither adenosine deaminase nor 8-phenyltheophylline attenuated the increase in coronary blood flow or the decrease of coronary vascular resistance during exercise. Neither agent altered the relation between myocardial oxygen consumption and coronary blood flow. Thus, although both adenosine deaminase and 8-phenyltheophylline antagonized coronary vasodilation in response to exogenous adenosine and blunted coronary reactive hyperemia, neither agent impaired coronary vasodilation associated with increased myocardial oxygen requirements produced by exercise. These findings fail to support a substantial role for adenosine in mediating coronary vasodilation during exercise.

Effects of atrial natriuretic peptide on coronary vascular resistance in the intact awake dog.

Atrial natriuretic peptide has been reported to cause vasoconstriction, vasodilation or no change of coronary vascular resistance in isolated perfused hearts or in open chest animal models. Because general anesthesia and acute surgical trauma may perturb baseline coronary hemodynamics and alter responses to experimental interventions, this study examined the effects of human atrial natriuretic peptide (arginine-102-tyrosine-126) and rat atriopeptin II (serine-103-arginine-125) on the coronary circulation of unsedated, awake dogs. Studies were performed in 12 chronically instrumented animals in which a surgically implanted electromagnetic flow probe and intracoronary catheter allowed measurement of left circumflex coronary blood flow during intraarterial administration of the atrial natriuretic peptides. Bolus doses of both human atrial natriuretic peptide and rat atriopeptin II produced dose-dependent coronary vasodilation; the threshold for coronary vasodilation was 0.2 micrograms/kg body weight for both agents. Coronary vasodilation produced by human atrial natriuretic peptide was not antagonized by adenosine receptor blockade or by cyclooxygenase inhibition with indomethacin. Thus, atrial natriuretic peptides produced dose-dependent coronary vasodilation in intact awake dogs that was not dependent on adenosine-mediated or prostaglandin-mediated mechanisms.

Effects of atrial natriuretic peptide in the canine coronary circulation.

Atriopeptin II has been reported to cause profound coronary vasoconstriction in the isolated perfused guinea pig heart and in the blood perfused canine heart. Consequently, this study was carried out to examine possible mechanisms by which vasomotor effects of human atrial natriuretic peptide (ANP) occur in the canine coronary circulation. Bolus dosages of ANP were administered into the left circumflex coronary artery of in situ dog hearts perfused at constant flow rate. ANP produced dose-related coronary vasodilation with a threshold dosage of 2 ng/kg; a dosage of 2 micrograms/kg caused a 27 +/- 4% decrease in coronary vascular resistance. Coronary vasodilation produced by ANP was not altered by beta-adrenergic blockade with propranolol (1 mg/kg i.v.). In addition, neither adenosine receptor blockade with 8-phenyltheophylline (5 mg/kg i.v.) nor cyclooxygenase inhibition with indomethacin (5 mg/kg i.v.) significantly altered the response to intra-arterial ANP. These data demonstrate that in the in vitro blood perfused canine heart, ANP administered intra-arterially results in coronary vasodilation that does not utilize adenosine-dependent or prostaglandin-dependent mechanisms.

Myocardial blood flow in left ventricular hypertrophy developing in young and adult dogs.

This study was performed to test the hypothesis that growth of coronary vasculature would be facilitated if myocardial hypertrophy occurred during the period of normal body growth rather than in mature adult animals. Left ventricular hypertrophy was produced by banding the ascending aorta in eight young dogs 7 wk of age and in nine adult dogs. Adult dogs were studied 2 mo after aortic banding, whereas young dogs were allowed to grow to adulthood before study. Left ventricular weight-to-body weight ratios were increased to 6.88 +/- 0.36 g/kg in the young dogs and 6.64 +/- 0.47 in adult dogs; both were significantly greater than seven normal control animals (4.32 +/- 0.05; each P less than 0.01). Myocardial blood flow per gram measured with microspheres during quiet resting conditions was significantly higher in young dogs with left ventricular hypertrophy than in normal dogs. Myocardial blood flow rates during maximum coronary vasodilation with adenosine (4 mumol X kg-1 X min-1 iv) were similar in all three groups. However, since mean coronary perfusion pressure was higher in the dogs with aortic banding, minimum coronary vascular resistance per gram of myocardium was significantly higher in both young (21.1 +/- 3.1 mmHg X ml-1 X min X g) and adult dogs with left ventricular hypertrophy (21.8 +/- 2.2) than in the normal dogs (16.8 +/- 3.1; each P less than 0.01). Mean coronary vascular resistance for the total left ventricle was similar in all three groups of animals, suggesting that growth of coronary vasculature did not occur as the myocardium underwent hypertrophy.(ABSTRACT TRUNCATED AT 250 WORDS)

Alterations of myocardial blood flow associated with experimental canine left ventricular hypertrophy secondary to valvular aortic stenosis.

Experimental renovascular hypertension or supravalvular aortic constriction results in left ventricular hypertrophy and impaired minimum coronary vascular resistance. However, these experimental models expose the coronary arteries to increased intra-arterial pressure, so that hypertensive vascular changes might be responsible for the impaired minimum coronary resistance. This study was performed to test the hypothesis that left ventricular hypertrophy in the absence of increased coronary pressure results in abnormalities of myocardial perfusion. Aortic valve stenosis was produced by plication of the noncoronary aortic cusp of 11 dogs at 6-8 weeks of age. Studies were carried out when the animals reached adulthood; mean left ventricular:body weight ratio was 7.1 +/- 0.4 as compared to 4.4 +/- 0.3 g/kg in 11 normal dogs (P less than 0.01). Under quiet resting conditions, myocardial blood flow measured with microspheres was significantly greater than normal in dogs with aortic stenosis. However, during maximum coronary vasodilation with adenosine, mean left ventricular blood flow in dogs with hypertrophy (3.29 +/- 0.39) was substantially less than in normal dogs (6.19 +/- 0.54 ml/min per g; P less than 0.01), whereas minimum coronary resistance was increased from 14.1 +/- 1.7 in normal dogs to 23.7 +/- 5.4 mmHg. min X g/ml (P less than 0.01). To examine the response of myocardial perfusion to cardiac stress, blood flow was measured during pacing at 200 and 250 beats/min. Compared with normal dogs, animals with hypertrophy had a subnormal increase in myocardial blood flow during tachycardia; this perfusion deficit was most marked in the subendocardium. These data demonstrate that left ventricular hypertrophy alone, without increased coronary artery pressure, is associated with impaired minimum coronary vascular resistance and with abnormalities of myocardial blood flow during pacing stress.