Pressure natriuresis in isolated kidneys from hypertension-prone and hypertension-resistant rats (Dahl rats)11Dr. Dahl, with whom we were collaborating, died just as this work was beginning. We wish to dedicate this paper to his memory.

Pressure natriuresis in isolated kidneys from hypertension-prone and hypertension-resistant rats (Dahl rats). Dahl described a strain of rats with genetically controlled propensities for hypertension. Chronic excess salt feeding increased blood pressure in sensitive (S) rats, whereas resistant rats (R) remain normotensive. We tested the pressure natriuretic function (urinary sodium excretion versus perfusion pressure) in isolated kidneys perfused with a cellular medium: in sodium-restricted normotensive sensitive (S0) and resistant (R0) animals; in sensitive rats receiving a high-salt diet for 3 weeks (S3); and in both S and R animals exposed to excess sodium for 7 weeks (R7 and S7). The aim of these studies was to determine if a preset alteration of the pressure natriuretic function might be present in S animals prior to the development of hypertension. Systolic blood pressure in S0, S3, and S7animals were 123 ± 4, 136 ± 2, and 162 ± 4mm Hg, respectively, whereas that of R0 and R7 were 121 ± 5 and 126 ± 5mm Hg. An increase of the perfusion pressure of isolated kidneys from 105 to 185mm Hg in stepwise fashion resulted in a pressure natriuresis whose slope was similar in R0 and S0 animals. Of interest was that the pressure natriuretic function slope of kidneys from R0(low sodium) and R7 (high sodium) rats was as predicted by the Guyton system analysis of normal blood pressure control. Micropuncture of the proximal nephrons demonstrated that the origin of the natriuresis resulted from a site beyond the accessible proximal tubule. Results from S7 kidneys contrasted with all others in that the natriuretic response was depressed (P < 0.01), which resulted from significantly lower filtration rates at higher perfusion pressures. We concluded (1) in normal R rats, the pressure natriuretic function is that predicted by the Guyton hypothesis, (2) Dahl S animals have no preset abnormality of this function until hypertension is present for some time, and (3) a depression of the pressure natriuretic function may aggravate hypertension in S rats once high blood pressure has persisted.Natriurèse de pression dans les reins isolés provenant de rats de Dahl sensibles ou résistants à l'hypertension. Dahl a décrit une souche de rats ayant une propension génétique à l'hypertension. L'administration d'une alimentation riche en sel augmente la pression artérielle chez les rats sensibles (S) alors que les rats résistants (R) restent normotendus. Nous avons étudié la natriurèse de pression (excrétion urinaire de sodium en fonction de la pression de perfusion) dans des reins isolés perfuses avec un milieu cellulaire provenant de rats normotendus S0 et R0 soumis à une restriction de sodium, de rats sensibles ayant reçu une alimentation riche en sel pendant trois semaines (S3) et de rats S et R exposés à un excès de sel pendant 7 semaines (R7 et S7). Le but de ces études est d'établir l'existence éventuelle d'une modification de la relation pression natriurèse avant le développement de l'hypertension. Les pressions systoliques des rats, S0, S3, et S7 étaient de 123 ± 4, 136 ± 2, et 162 ± 4mm Hg, respectivement, alors que celles de R0 et R7 étaient de 121 ± 5 et 126 ± 5mm Hg. Une augmentation de la pression de perfusion de reins isolés de 105 à 185mm Hg, par paliers, a eu pour résultat une natriurèse de pression dont la pente était la même chez R0 et S0. Il est intéressant de remarquer que la pente de cette relation pour les reins R0 (sodium bas) et R7 (sodium élevé) est celle qui est prévue par l'analyse de Guyton du contrôle normal de la pression artérielle. Des microponctions des néphrons proximaux ont montré que l'origine de la natriurèse est en aval du tuble proximal accessible. Les résultats des reins S7 ont été différents de tous les autres en ce sens que la réponse natriurétique a été déprimée (P < 0,001) en raison des débits de filtration significativement plus faibles à des pressions de perfusion plus élevées. Nous concluons: (1) chez les rats R normaux la relation pression-natriurèse est celle prédite par l'hypothèse de Guyton; (2) les animaux Dahl S n'ont pas d'anomalie préexistante de cette fonction; (3) une dépression de la relation natirurèse-pression peut aggraver l'hypertension chez les rats S une fois que la pression artérielle élevée a persisté

TUMOR MARKERS IN BONE MARROW IN PATIENTS WITH PROSTATIC CANCER

We compared prostatic specific acid phosphatase (PAP), prostatic specific antigen (PA) and γ-seminoprotein (γ-SM) levels between bone marrow and serum for the purpose of assessing of the usefulness of these tumor markers in early detection of bone metastasis in cases with prostatic cancer. Thirty-three patients were entered into this study. Of the patients, 20 had prostatic cancer including 11 with bone metastasis, and 13 patients had benign prostatic hypertrophy (BPH) served as controls. It seemed unlikely that bone marrow PAP, PA and γ-SM are more useful than their serum levels for detection of bone metastasis of prostatic cancer. Because correlation between bone marrow and serum levels of each marker was observed not only in cases with prostate cancer accompanied by bone metastasis but also in metastasis-free prostatic cancer and BPH cases, it seems likely that PAP, PA and γ-SM in bone marrow circulate from peripheral blood rather than from bone metastasis of prostatic cancer

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19

Symptomatic periesophageal vagal nerve injury by different energy sources during atrial fibrillation ablation

BackgroundSymptomatic gastric hypomotility (SGH) is a rare but major complication of atrial fibrillation (AF) ablation, but data on this are scarce.ObjectiveWe compared the clinical course of SGH occurring with different energy sources.MethodsThis multicenter study retrospectively collected the characteristics and clinical outcomes of patients with SGH after AF ablation.ResultsThe data of 93 patients (67.0 ± 11.2 years, 68 men, 52 paroxysmal AF) with SGH after AF ablation were collected from 23 cardiovascular centers. Left atrial (LA) ablation sets included pulmonary vein isolation (PVI) alone, a PVI plus a roof-line, and an LA posterior wall isolation in 42 (45.2%), 11 (11.8%), and 40 (43.0%) patients, respectively. LA ablation was performed by radiofrequency ablation, cryoballoon ablation, or both in 38 (40.8%), 38 (40.8%), and 17 (18.3%) patients, respectively. SGH diagnoses were confirmed at 2 (1–4) days post-procedure, and 28 (30.1%) patients required re-hospitalizations. Fasting was required in 81 (92.0%) patients for 4 (2.5–5) days; the total hospitalization duration was 11 [7–19.8] days. After conservative treatment, symptoms disappeared in 22.3% of patients at 1 month, 48.9% at 2 months, 57.6% at 3 months, 84.6% at 6 months, and 89.7% at 12 months, however, one patient required surgery after radiofrequency ablation. Symptoms persisted for &gt;1-year post-procedure in 7 patients. The outcomes were similar regardless of the energy source and LA lesion set.ConclusionsThe clinical course of SGH was similar regardless of the energy source. The diagnosis was often delayed, and most recovered within 6 months, yet could persist for over 1 year in 10%