Nightlife clusters of coronavirus disease in Tokyo between March and April 2020.

We analysed associations between exposure to nightlife businesses and severe acute respiratory syndrome coronavirus 2 PCR test results at a tertiary hospital in Tokyo between March and April 2020. A nightlife group was defined as those who had worked at or visited the businesses. We included 1517 individuals; 196 (12.9%) were categorised as the nightlife group. After propensity score matching, the proportion of positive PCR tests in the nightlife group was significantly higher than that in the non-nightlife group (nightlife, 63.8%; non-nightlife, 23.0%; P < 0.001). An inclusive approach to mitigate risks related to the businesses needs to be identified.

The efficacy of the direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in the pediatric ward of a tertiary medical facility without a pediatric antimicrobial stewardship program.

Antimicrobial stewardship programs (ASPs) have been introduced in most hospital complexes; however, they are not always useful for pediatric patients. The aim of this study is to investigate the efficacy of direct clinical intervention for infectious diseases by a pediatric infectious disease specialist in a tertiary medical facility without pediatric ASP. This retrospective study included 1,821 patients who were hospitalized in the pediatric ward of a large metropolitan hospital from 2010 to 2015. The clinical course, the use of intravenous antimicrobial agents and the results of a microbiological analysis were compared between the period after the beginning of direct intervention by the specialist (post-intervention period) and the previous period (pre-intervention period). In the post-intervention period, the proportion of the patients who received intravenous antimicrobial agents, the number of antimicrobial agents used for each episode, and the proportion of episodes in which an antimicrobial agent was re-administrated were significantly lower (P = 0.006, P = 0.004, P = 0.036, respectively), and the duration of antimicrobial treatment was significantly shorter (P < 0.001). In addition, narrower spectrum antimicrobial agents were used, and the incidence of meropenem-sensitive Pseudomonas aeruginosa significantly increased (P = 0.037) in the post-intervention period. There was no change of mortality between the two periods. Direct clinical intervention by a pediatric infectious diseases specialist is useful for the treatment of infectious diseases in the pediatric ward of a tertiary medical facility without a pediatric ASP. The creation of a pediatric ASP is recommended in hospital complexes.

Remineralization of artificial enamel lesions by theobromine.

OBJECTIVE: This study investigated the remineralization potential of theobromine in comparison to a standard NaF dentifrice. METHODS: Three tooth blocks were produced from each of 30 teeth. Caries-like lesion was created on each block using acidified gel. A smaller block was cut from each block for baseline scanning electron microscopy imaging and electron-dispersive spectroscopy (EDS) analysis for surface Ca level. A tooth slice was cut from each lesion-bearing block for transverse microradiography (TMR) quantification of baseline mineral loss (Δz) and lesion depth (LD). Then baseline surface microhardness (SMH) of each lesion was measured. The three blocks from each tooth were assigned to three remineralizing agents: (1) artificial saliva; (2) artificial saliva with theobromine (0.0011 mol/l), and (3) NaF toothpaste slurry (0.0789 mol/l F). Remineralization was conducted using a pH cycling model with storage in artificial saliva. After a 28-day cycle, samples were analyzed using EDS, TMR, and SMH. Intragroup comparison of pre- and posttest data was performed using t tests (p < 0.05). Intergroup comparisons were performed by post hoc multistep comparisons (Tukey). RESULTS: SMH indicated significant (p < 0.01) remineralization only with theobromine (38 ± 32%) and toothpaste (29 ± 16%). With TMR (Δz/lD), theobromine and toothpaste exhibited significantly (p < 0.01) higher mineral gain relative to artificial saliva. With SMH and TMR, remineralization produced by theobromine and toothpaste was not significantly different. With EDS, calcium deposition was significant in all groups, but not significantly different among the groups (theobromine 13 ± 8%, toothpaste 10 ± 5%, and artificial saliva 6 ± 8%). CONCLUSION: The present study demonstrated that theobromine in an apatite-forming medium can enhance the remineralization potential of the medium.

Management of sleep-time masticatory muscle activity using stabilisation splints affects psychological stress.

To treat sleep bruxism (SB), symptomatic therapy using stabilisation splints (SS) is frequently used. However, their effects on psychological stress and sleep quality have not yet been examined fully. The objective of this study was to clarify the effects of SS use on psychological stress and sleep quality. The subjects (11 men, 12 women) were healthy volunteers. A crossover design was used. Sleep measurements were performed for three consecutive days or longer without (baseline) or with an SS or palatal splint (PS), and data for the final day were evaluated. We measured masseter muscle activity during sleep using portable electromyography to evaluate SB. Furthermore, to compare psychological stress before and after sleep, assessments were made based on STAI-JYZ and the measurement of salivary chromogranin A. To compare each parameter among the three groups (baseline, SS and PS), Friedman's and Dunn's tests were used. From the results of the baseline measurements, eight subjects were identified as high group and 15 as low group. Among the high group, a marked decrease in the number of bruxism events per hour and an increase in the difference in the total STAI Y-1 scores were observed in the SS group compared with those at baseline (P < 0·05). No significant difference was observed in sleep stages. SS use may be effective in reducing the number of SB events, while it may increase psychological stress levels, and SS use did not apparently influence sleep stages.

Cardiovascular anomaly, impaired actin bundling and resistance to Src-induced transformation in mice lacking p130Cas.

p130Cas (Cas), the protein encoded by the Crkas gene (also known as Cas), is an adaptor molecule with a unique structure that contains a Src homology (SH)-3 domain followed by multiple YXXP motifs and a proline-rich region. Cas was originally cloned as a highly tyrosine-phosphorylated protein in cells transformed by v-Src (refs 2,3) or v-Crk (ref. 4) and has subsequently been implicated in a variety of biological processes including cell adhesion, cell migration, growth factor stimulation, cytokine receptor engagement and bacterial infection. To determine its role in vivo, we generated mice lacking Cas. Cas-deficient embryos died in utero showing marked systemic congestion and growth retardation. Histologically, the heart was poorly developed and blood vessels were prominently dilated. Electron microscopic analysis of the heart revealed disorganization of myofibrils and disruption of Z-disks. In addition, actin stress fiber formation was severely impaired in Cas-deficient primary fibroblasts. Moreover, expression of activated Src in Cas-deficient primary fibroblasts did not induce a fully transformed phenotype, possibly owing to insufficient accumulation of actin cytoskeleton in podosomes. These findings have defined Cas function in cardiovascular development, actin filament assembly and Src-induced transformation.

Observer performance in diagnosing osteoporosis by dental panoramic radiographs: results from the osteoporosis screening project in dentistry (OSPD).

Mandibular cortical erosion detected on dental panoramic radiographs (DPRs) may be useful for identifying women with osteoporosis, but little is known about the variation in diagnostic efficacy of observers worldwide. The purpose of this study was to measure the accuracy in identifying women at risk for osteoporosis in a worldwide group of observers using DPRs. We constructed a website that included background information about osteoporosis screening and instructions regarding the interpretation of mandibular cortical erosion. DPRs of 100 Japanese postmenopausal women aged 50 years or older who had completed skeletal bone mineral measurements by dual energy X-ray absorptiometry were digitized at 300 dpi. These were displayed on the website and used for the evaluation of diagnostic efficacy. Sixty observers aged 25 to 66 years recruited from 16 countries participated in this study. These observers classified cortical erosion into one of three groups (none, mild to moderate, and severe) on the website via the Internet, twice with an approximately 2-week interval. The diagnostic efficacy of the Osteoporosis Self-Assessment Tool (OST), a simple clinical decision rule based on age and weight, was also calculated and compared with that of cortical erosion. The overall mean sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the 60 observers in identifying women with osteoporosis by cortical erosion on DPRs were 82.5, 46.2, 46.7, and 84.0%, respectively. Those same values by the OST index were 82.9, 43.1, 43.9, and 82.4%, respectively. The intra-observer agreement in classifying cortical erosion on DPRs was sufficient (weighted kappa values>0.6) in 36 (60%) observers. This was significantly increased in observers who specialized in oral radiology (P<0.05). In the 36 observers with sufficient intra-observer agreement, the overall mean sensitivity, specificity, PPV, and NPV in identifying women with osteoporosis by any cortical erosion were 83.5, 48.7, 48.3, and 85.7%, respectively. The mean PPV and NPV were significantly higher in the 36 observers with sufficient intra-observer agreement than in the 24 observers with insufficient intra-observer agreement. Our results reconfirm the efficacy of cortical erosion findings in identifying postmenopausal women at risk for osteoporosis, among observers with sufficient intra-observer agreement. Information gathered from radiographic examination is at least as useful as that gathered from the OST index.

Deficiency of CIZ, a nucleocytoplasmic shuttling protein, prevents unloading-induced bone loss through the enhancement of osteoblastic bone formation in vivo.

Disuse osteoporosis is a major cause to increase the risk of fractures in bed-ridden patients whose numbers are increasing in our modern society. However, the mechanisms underlying the sensing of mechanical stress in bone are largely unknown. CIZ localizes at cell adhesion plaque and transfers into nuclear compartments and activates promoters of the genes encoding enzymes, which degrade matrix proteins to link signals from the cell adhesion site to nuclear events. We examined whether this nucleocytoplasmic shuttling protein would be involved in mediation of mechanical stress signaling. Unloading based on tail suspension reduced bone volume in wild-type mice. In contrast, CIZ-deficient mice revealed suppression in such reduction of bone mass due to unloading. Histomorphometric analysis revealed that unloading suppressed the levels of osteoblastic bone formation parameters, and such suppression of bone formation parameters was blocked by CIZ-deficiency. Osteoclastic bone resorption parameters were similar regardless of CIZ-deficiency after 2-week unloading. Mineralized nodule formation in the cultures of bone marrow cells obtained from the bone of mice subjected to unloading was suppressed in wild-type mice. CIZ deficiency blocked such reduction in nodule formation induced by unloading. These data indicated that nucleocytoplasmic shuttling protein, CIZ, plays a pivotal role in the response of bone mass in unloading condition.

Requirements for localization of p130cas to focal adhesions.

p130cas (Cas) is an adapter protein that has an SH3 domain followed by multiple SH2 binding motifs in the substrate domain. It also contains a tyrosine residue and a proline-rich sequence near the C terminus, which are the binding sites for the SH2 and SH3 domains of Src kinase, respectively. Cas was originally identified as a major tyrosine-phosphorylated protein in v-Crk- and v-Src-transformed cells. Subsequently, Cas was shown to be inducibly tyrosine phosphorylated upon integrin stimulation; it is therefore regarded as one of the focal adhesion proteins. Using an immunofluorescence study, we examined the subcellular localization of Cas and determined the regions required for its localization to focal adhesions. In nontransformed cells, Cas was localized predominantly to the cytoplasm and partially to focal adhesions. However, in 527F-c-Src-transformed cells, Cas was localized mainly to podosomes, where the focal adhesion proteins are assembled. The localization of Cas to focal adhesions was also observed in cells expressing the kinase-negative 527F/295M-c-Src. A series of analyses with deletion mutants expressed in various cells revealed that the SH3 domain of Cas is necessary for its localization to focal adhesions in nontransformed cells while both the SH3 domain and the C-terminal Src binding domain of Cas are required in 527F-c-Src-transformed cells and fibronectin-stimulated cells. In addition, the localization of Cas to focal adhesions was abolished in Src-negative cells. These results demonstrate that the SH3 domain of Cas and the association of Cas with Src kinase play a pivotal role in the localization of Cas to focal adhesions.

CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases.

p130(cas) (Cas) is a docking protein that contains an SH3 domain and multiple tyrosine residues. p130(cas) is located at focal adhesions, is tyrosine phosphorylated in response to integrin stimulation, and is thought to transmit signals, via c-Crk and other proteins, for the remodeling of actin stress fibers and cell movement. In a search for the ligands of the SH3 domain of p130(cas) by far-Western screening, we cloned a novel protein named CIZ (for Cas-interacting zinc finger protein). CIZ consists of the following: a putative leucine zipper; a serine/threonine-rich region; a proline-rich sequence; five, six, or eight Krüppel-type C(2)H(2) zinc fingers; and the glutamine-alanine repeat. CIZ binds Cas in cells and is located in the nucleus and at focal adhesions. We showed that CIZ is a nucleocytoplasmic shuttling protein, by using the transient interspecies heterokaryon formation assay. In order to search for the targets of CIZ in nucleus, we determined the DNA binding consensus of CIZ as (G/C)AAAAA(A) by cyclic amplification and selection of targets analysis. The consensus-like sequences are found in several promoters of matrix metalloproteinases (MMPs), which are the enzymes used to degrade the extracellular matrix proteins. CIZ binds to a consensus-like sequence in the MMP-1 (collagenase) promoter. Overexpression of CIZ upregulates the transcriptions from MMP-1, MMP-3 (stromelysin), and MMP-7 (matrilysin) promoters, and this transactivation was enhanced in the presence of Cas. Furthermore, the stable overexpression of CIZ promoted the production of MMP-7 in culture medium. In summary, CIZ, a novel zinc finger protein, binds Cas, is a nucleocytoplasmic shuttling protein, and regulates the expression of MMPs.

Association of insulin receptor substrate proteins with Bcl-2 and their effects on its phosphorylation and antiapoptotic function.

Insulin receptor substrate (IRS) proteins are docking proteins that couple growth factor receptors to various effector molecules, including phosphoinositide-3 kinase, Grb-2, Syp, and Nck. Here we show that IRS-1 associates with the loop domain of Bcl-2 and synergistically up-regulates antiapoptotic function of Bcl-2. IRS-2 but not IRS-3 binds to Bcl-2, and IRS-1 associates with Bcl-XL but not with Bax or Bik. Overexpression of IRS-1 suppresses phosphorylation of Bcl-2 induced by stimulation with insulin, and the hypophosphorylation may lead to its enhanced antiapoptotic activity. The binding site for Bcl-2 is located on the carboxyl half-domain of IRS-1. IRS-3, which lacks the corresponding region, dominant-negatively abrogates the survival effects of IRS-1 and Bcl-2. For the antiapoptotic activity of IRS-1, binding to Bcl-2 is more critical than activating phosphoinositide-3 kinase. Our results indicate that IRS proteins transmit signals from the insulin receptor to Bcl-2, thus regulating cell survival probably through regulating phosphorylation of Bcl-2.

Basic fibroblast growth factor in human prostate cancer cells.

To increase our understanding of the potential role of basic fibroblast growth factor (bFGF) in malignant progression of prostate cancer, we determined the production of bFGF, the expression of FGF receptor (flg), and the response to exogenous bFGF in LNCaP, DU 145, and PC 3 cells. We observed that these three prostate cancer cell lines, which differed in their dependence on androgens for growth in vitro and in their in vivo behavior in nude mice, could be distinguished as follows: (a) androgen-sensitive LNCaP cells, which do not metastasize in nude mice, did not produce measurable amounts of bFGF, expressed small but measurable amounts of FGF receptor mRNA, and did respond to exogeneous bFGF; (b) androgen-insensitive, moderately metastatic DU 145 cells did produce measurable amounts of biologically active bFGF, expressed large amounts of FGF receptor mRNA, and responded to exogeneous bFGF and the heparin-binding fractions from DU 145 cell extracts; (c) androgen-insensitive and highly metastatic PC3 cells also produced measurable amounts of bFGF but did not demonstrate a growth response to either the heparin-binding fractions from PC3 cell extracts or exogenous bFGF, even though large amounts of FGF receptor mRNA were expressed in PC 3 cells. These results suggest the possibility that differences in production of, and response to, bFGF may be associated with different biological behavior.

Comparison of Cosmesis and Body Image After Laparoendoscopic Single-Site Versus Conventional Laparoscopic Donor Nephrectomy.

BACKGROUND: This study used a questionnaire to objectively assess the body image of donors who underwent conventional laparoscopic donor nephrectomy (L-DN) or laparoscopic single-site donor nephrectomy (LESS-DN). Surgical outcomes were compared between the two groups. METHODS: Twenty patients underwent L-DN and 20 underwent LESS-DN. The postoperative outcomes of the two approaches were retrospectively compared and evaluated for differences in cosmesis and body image. The questionnaire comprised a body image questionnaire, including a body image scale (BIS) and cosmetic scale (CS), and a photo-series questionnaire (PSQ). A higher score indicated a more favorable assessment. Pain was assessed by comparing the number of times an analgesic was administered during hospitalization. RESULTS: There were no significant differences in operative outcomes between L-DN and LESS-DN. The average BIS score (maximum possible, 20 points) was 18.5 points for patients who underwent L-DN and 19.5 points for patients who underwent LESS-DN (P = .025). Patients who underwent L-DN had a median CS score (maximum possible, 24 points) of 17.5 points, whereas patients who underwent LESS-DN had a median CS score of 19.0 points (P = .113). The average PSQ score was 7.1 points for patients who underwent L-DN and 8.8 points for patients who underwent LESS-DN (P = .01). Patients who underwent LESS-DN were administered an analgesic was significantly number of times less than patients who underwent DN (P = .01). CONCLUSIONS: LESS-DN results in a better body image and better cosmetic appearance than does L-DN, indicating the clinical usefulness of LESS-DN.

Characterization of the kinase activity essential for tyrosine phosphorylation of p130Cas in fibroblasts.

The cellular transformation by v-Src or v-Crk induces tyrosine phosphorylation of a common substrate molecule, p130Cas (Cas), which tightly binds these oncoproteins in vivo. From its structure, Cas is deduced to be an ideal substrate for Src family kinases and Abl kinase. The tyrosine kinase activity associated with Cas was analysed using mouse variant fibroblasts lacking at least one of tyrosine kinases. In normal fibroblasts, Cas is associated with a significant level of tyrosine kinase activity which efficiently phosphorylates Cas in vitro. The Cas-associated tyrosine kinase activity was remarkably elevated in Csk-/- cells, which resulted in hyperphosphorylation of cellular Cas. The associated kinase activity was slightly increased in Src-/- cells whereas not significantly changed in Abl-/- nor Fak-/- cells. On the contrary, the Cas-associated kinase activity was remarkably decreased in Fyn-/- cells. At the same time, association of Cas with Fyn kinase in vitro was most obviously detected in normal fibroblasts as well as Csk-/- cells. Transient expression of v-Crk induced elevation of the Cas-associated kinase activity in all of these cell lines except the primary culture of Fyn-/- fibroblasts. These results indicate that Fyn kinase plays an essential role in v-Crk-mediated phosphorylation of Cas.

The phosphatidylinositol 3' kinase pathway is required for the survival signal of leukocyte tyrosine kinase.

Leukocyte tyrosine kinase (LTK) is a receptor tyrosine kinase which belongs to the insulin receptor superfamily and is mainly expressed in pre-B lymphocytes and neuronal tissues. Recently, we demonstrated that LTK utilizes Shc and IRS-1 as two major substrates and while both equally activate the Ras pathway, only IRS-1 suppresses apoptosis of hematopoietic cells, suggesting the existence of another unidentified signaling pathway downstream of IRS-1, which is relevant to the anti-apoptotic activity. In the present study, we found that wortmannin, a specific inhibitor of phosphatidylinositol 3' (PI3)-kinase, abolished the survival effects of LTK. Although c-Cbl is found to be phosphorylated by LTK and therefore is a second candidate linking LTK with the PI3-kinase pathway along with IRS-1, we found that the p85 subunit of PI3 kinase directly binds to tyrosine 753 of LTK, which is located within a YXXM motif, a consensus binding amino acid sequence for the SH2 domain of p85, but fails to bind to IRS-1 or c-Cbl. Ba/F3 cells which stably express the EGF receptor-LTK chimeric receptor carrying a mutation at tyrosine 753 fell into apoptotic death even in the presence of EGF, indicating that the PI3 kinase pathway is required for the survival effects of LTK.

On the accessibility and selection of the initiator site of mRNA in protein synthesis.

The specificity of the cell-free system of Escherichia coli for mRNA was examined, and the "accessibility" of some natural and synthetic RNAs to the ribosomes was determined by measurement of AcPhe-tRNA and fMet-tRNA binding, AcPhe-puromycin and fMet-puromycin formation, and polypeptide synthesis. The E. coli system effectively initiates the translation of various synthetic RNAs with AcPhe-tRNA or fMet-tRNA under conditions optimal for the translation of viral RNA. Poly(A,G,U) is accessible to the ribosomes according to all of the above criteria. Poly(A,C,G,U), 23 S rRNA, R17 RNA, and MS2 RNA, on the other hand, show limited accessibility when tested for initiator tRNA binding, or for AcPhe-puromycin and fMet-puromycin formation. MS2 and R17 RNA, but not poly(A,C,G,U) and 23 S rRNA, show accessibility when measured by polypeptide synthesis. The results suggest that, except at initiator sites of natural mRNA, an RNA containing about equal amounts of all four bases is inaccessible to E. coli ribosomes for polypeptide synthesis. Rate constants obtained for fMet-tRNA binding with MS2 RNA, poly(A,G,U), and poly(C,G,U) indicate that the ribosomes do not have any special affinity for the viral RNA. Thus, the selection of the initiator site in protein synthesis may be critically determined more by the accessibility of the initiator codon than by ribosomal recognition of the site.

Estimation of left ventricular elastance without altering preload or afterload in the conscious dog.

OBJECTIVE: The aim was to determine the slope (EES) of the left ventricular end systolic pressure-volume line (ESPVL) without altering preload or afterload in conscious dogs. METHODS: Dogs (n = 10) were instrumented to determine left ventricular volume from ultrasonic left ventricular internal dimensions, and to measure left ventricular pressure using a micromanometer. Studies were performed one to two weeks after instrumentation while the animals were conscious. ESPVL was determined from variably loaded left ventricular pressure-volume (P-V) loops generated by the vena caval occlusion. Contractile state was increased by intravenous dobutamine (8 micrograms.kg-1 x min-1) and decreased by intravenous verapamil (10 mg) given after autonomic blockade. From a single normally ejecting beat, we calculated EES-single beat (mm Hg.ml-1) as peak isovolumetric pressure (Pmax) minus end systolic pressure divided by stroke volume. Sunagawa's technique was used to estimate Pmax by fitting the pressure during the isovolumetric contraction and relaxation as: P(t) = 1/2 X Piso[1-cos(omega t+c)]+LVEDP, where Piso = peak isovolumetric developed pressure, LVEDP = left ventricular end diastolic pressure, c = constant accounting for variations in phase angle, and omega = 2 pi/T in which T is duration of contraction. RESULTS: After dobutamine, EES increased, from 8.9(SEM 0.8) to 12.5(1.0) mm Hg.ml-1 (p < 0.05), and EES-single beat increased from 9.1(0.9) to 12.0(1.4) mm Hg.ml-1 (p < 0.05). Conversely, after verapamil, EES decreased, from 11.1(1.2) to 6.3(1.1) mm Hg.ml-1, (p < 0.05), and EES-single beat also decreased, from 9.6(1.0) to 7.3(1.2) mm Hg.ml-1, (p < 0.05). CONCLUSIONS: EES calculated from one beat is similar to EES determined from variably loaded left ventricular loops and responds appropriately to inotropic stimulation. This technique provides a reasonable method to calculate EES from left ventricular pressure and stroke volume without altering preload or afterload.

Differential effects of positive end expiratory pressure and cardiac tamponade on left-right ventricular mechanical function in the dog.

OBJECTIVE: The aim was to examine the hypothesis that an increased coupling occurs between the ventricles during tamponade via a ventricular-pericardial-ventricular interaction, but that ventricular coupling would be unaltered or reduced with positive end expiratory pressure (PEEP). METHODS: An in situ arrested, canine heart preparation was used. Changes in left and right ventricular pressure (dPl, dPr) and volume (dVl, dVr) caused by increasing the volume of the other ventricle were measured at normal and at matched levels of raised pericardial pressures (Pp) caused by 20 cm H2O PEEP and by tamponade. RESULTS: With PEEP, the coupling between the ventricles was unaltered when compared to control. With tamponade, dPl/dPr, dVl/dPr, dPr/dPl, and dVr/dPl increased significantly (p less than 0.05) by 0.21 (SEM 0.03, unitless), 0.45(0.04) ml.mm Hg-1, 0.18(0.03), and 0.28(0.04) ml.mm Hg-1 respectively. CONCLUSIONS: Augmented ventricular interdependence occurs during tamponade but not with PEEP, which may help to explain the different haemodynamic patterns observed under these conditions.

Effects of increased pericardial pressure on the coupling between the ventricles.

STUDY OBJECTIVE: The mechanical coupling between the ventricles occurs directly through the myocardium (ventricular-ventricular coupling) and indirectly through the pericardium (ventricular-pericardial-ventricular coupling). We postulated that the magnitude of ventricular-pericardial-ventricular coupling would increase at high pericardial pressures, while ventricular-ventricular coupling would be unaltered. DESIGN: Canine hearts were removed and placed in cold cardioplegic solution. Balloons were inserted into each ventricle and the left and right ventricular pressure (dP1, dPr) and volume (dV1, dVr) changes caused by increasing the pressure and volume of the other ventricle and by increasing pericardial pressure (dPp) were measured. EXPERIMENTAL MATERIALS: Hearts from 10 random source dogs, weight 12.5-18 kg, were used. MEASUREMENT AND MAIN RESULTS: At control pericardial pressure levels, the magnitude of the pericardial-ventricular interactions was greater than the ventricular-ventricular interactions: dP1/dPp was significantly greater than dP1/dPr, at 0.71 (SEM 0.04), n = 6, v 0.18 (0.03), p less than 0.01, and dV1/dPp was significantly greater than dV1/dPr, at -0.83 (0.09) v -0.24 (0.06), p less than 0.05. Raising the pericardial pressure increased the mechanical coupling between the ventricles: dP1/dPr approximately, dV1/dPr approximately, dPr/dP1 approximately, and dVr/dP1 approximately increased significantly (p less than 0.05) by 0.48 (0.03), 0.67 (0.13), 0.38 (0.05), and 0.61 (0.09) respectively. This increased coupling occurred through pericardial pressure changes. If pericardial pressure was maintained constant, the coupling between the ventricles was unaltered. This same pattern was observed in four in situ experiments. For these experiments, at the raised pericardial pressure levels, dP1/dPr increased, from 0.51 (0.03) to 0.79 (0.01), p less than 0.05, if pericardial pressure was allowed to vary, but was unaltered with a constant pericardial pressure, at 0.42 (0.03) v 0.44 (0.04), p greater than 0.5. CONCLUSIONS: Ventricular interdependence was increased with raised pericardial pressure and this increased coupling was due primarily to an increased ventricular-pericardial-ventricular coupling. This increased coupling may help to explain the paradoxical pulse observed in cardiac tamponade.

Ventricular coupling via the pericardium: normal versus tamponade.

OBJECTIVE: The aim was to examine how regional variations in pericardial pressure affect the mechanical coupling between the ventricles. METHODS: Canine hearts from 14 dogs (14.5-18 kg) were removed and placed in cold cardioplegia solution. Balloons were inserted into the left and right ventricles and the atria. Pericardial pressure over the left ventricle (Pclv) and the right ventricle (Pcrv) was measured with thin balloon catheters. Ventricular and pericardial pressures were measured, and ventricular and pericardial coupling was calculated, under control conditions and with increases in pericardial tension and fluid. RESULTS: At baseline, regional differences in pericardial pressure occurred [Pclv > Pcrv, 4.0(SD 0.9) v 2.9(0.6) mm Hg, p < 0.05]. Ventricular coupling via the pericardium was defined as delta Pclv/delta Pcrv for right ventricular volume increases and delta Pcrv/delta Pclv for left ventricular volume increases. This ratio increased more after increasing right ventricular volume than after increasing left ventricular volume [delta Pclv/delta Pcrv > delta Pcrv/delta Pclv, 1.14(0.33) v 0.51(0.15), p < 0.05]. Increasing the pericardial tension by clamping the pericardium increased pericardial pressures, yet did not alter the regional variations in pressure [Pclv > Pcrv, 8.4(2.2) v 6.4(2.5) mm Hg, p < 0.05] or pericardial coupling [delta Pclv/delta Pcrv > delta Pclv/delta Pcrv, 1.18(0.46) v 0.54(0.16), p < 0.05]. In contrast, creating a mild tamponade increased pericardial pressures, eliminated regional differences in pressure, and altered the coupling between ventricles [delta Pclv/delta Pcrv approximately delta Pclv/delta Pcrv, 0.95(0.11) v 1.05(0.08), p = NS]. These regional differences in pericardial pressure might have a geometrical basis. In four in vivo canine experiments using cine magnetic resonance, the short axis radius of curvature for the right ventricle was greater than for the left ventricle [38.3(4.4) mm v 29.2(3.8) mm, p < 0.05]. CONCLUSIONS: The pericardium partially protects right ventricular filling: regional differences in pericardial pressure normally occurred with lower pericardial pressure over the right ventricle, and left to right ventricular coupling was less. This protection of right ventricular filling was lost with even a small pericardial effusion.