The endothelium-dependent vascular relaxation to acetylcholine (ACh) in spontaneously hypertensive rats (SHR) may be impaired because of an imbalance of endothelium-derived relaxing factor and contracting factor. However, the role of the endothelium-dependent hyperpolarization remains undetermined. We examined the ACh-induced hyperpolarization and its contribution to relaxation in arteries of SHR. Membrane potentials were recorded from the mesenteric artery trunk of 6-8-month-old male SHR and also Wistar-Kyoto (WKY) rats. Endothelium-dependent hyperpolarization to ACh was unaffected by NG-nitro-L-arginine, indomethacin, or glibenclamide; was reduced by tetraethylammonium or high K' solution; and was enhanced by low K' solution or methylene blue, thereby indicating that hyperpolarization is not mediated by nitric oxide (endothelium-derived relaxing factor) but is presumably mediated by a hyperpolarizing factor and is due to an opening of K' channels that probably differ from the ATP-sensitive ones. Hyperpolarizations to ACh were markedly reduced in SHR compared with findings in WKY rats (maximum, 8±1 versus 17±1 mV). In addition, under conditions of depolarization with norepinephrine (10-5 M), the ACh-induced hyperpolarization was even less and transient in SHR, while it was large and sustained in WKY rats (6±1 versus 29±2 mV

This study was undertaken to compare age-related changes in endothelium-dependent vascular responses in both hypertensive and normotensive rats. Aorta from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) aged 4-6 weeks (young), 3-6 months (adult), and 12-25 months (old) were examined for relaxation to acetylcholine, adenosine 5'-triphosphate (ATP), and sodium nitroprusside. Rubbed (endothelium denuded) aorta from all groups displayed neither relaxation nor contraction to acetylcholine. Maximal relaxation responses to acetylcholine were reduced progressively with increasing age in unrubbed aorta of both SHR and WKY rats. In addition, acetylcholine caused not only dose-dependent relaxations at lower concentrations but also increases in tension at higher concentrations in unrubbed aorta of old WKY rats as well as adult and old SHR. However, indomethacin completely inhibited the tension development. As a result, aorta treated with indomethacin demonstrated similar acetylcholine-induced, endothelium-dependent relaxations in all groups. The thromboxane A 2 synthetase inhibitor (E)-7-phenyl-7-(3-pyridyl)-6-heptanoic acid (CV-4151) partially but significantly depressed the increases in tension in aorta of old WKY rats. The degrees of endothelium-dependent relaxations to ATP and endothelium-independent relaxations to sodium nitroprusside were almost similar in all groups. These findings suggest that the release of or vascular responsiveness to endothelium-derived relaxing factor in the aorta is well maintained through senescence in both strains and that, in the aorta of not only SHR but also old normotensive WKY rats, the endothelium releases contracting factors that may be thromboxane A 2 and other vasoconstrictor prostanoids. (Hypertension 1989;14:542-548)

The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

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wave front propagation, especially in low voltage zones. By performing HDM mapping inside the PVAI lines after conventional encirclement lesions, we hoped to identify any RPs associated with ECs inside our PVAI lines. Thus, the purpose of this study was to determine the prevalence and number of ECs inside the PVAI lines after a conventional PVAI, and the effect of an EC ablation on the outcomes in patients with non-valvular paroxysmal (pAF), persistent (persAF), and long-lasting AF (LLAF). Methods Baseline Clinical Characteristics of the Patient GroupsThe present study was approved by the institutional review committee and ethics review board of our hospital, the Ethical Review Board of Steel Memorial Yawata Hospital. The procedures were followed in accordance with the Declaration of Helsinki and the ethical standards of the responsible committee on human experimentation. Moreover, we enrolled this study in an international registry of P ulmonary vein (PV) antrum isolation (PVAI) with radiofrequency catheter ablation (RFCA) has proven to be a useful strategy for atrial fibrillation patients (AF) worldwide. 1 To prevent initiating and maintaining AF, a complete PVAI should be a target of the AF treatment. 1 However, in spite of establishing complete PVAI lines, we rarely experience and encounter remaining potentials (RPs) inside our PVAI lines detected by high-density mapping (HDM). Then, when we perform pacing from the ablation catheter on the RPs inside our PVAI lines, we confirm that the pacing can capture RPs and conduct to the atrium. This finding indicates the existence of epicardial connection(s) (ECs) from inside the PVAI lines to the atrium after establishing complete conventional PVAI lines. The recent Intellamap Orion 2 (Boston Scientific Corporation, Marlborough, MA, USA) and Advisor TM HD Grid 3 (Abbott, Plymouth, MN, USA) advanced catheter technologies, which are directional HDM catheters, can not only identify low voltages and small local electrical signals, but also more importantly can capture the direction of the