Although suppression of sympathetic activity is suggested as one of the underlying mechanisms for the cardioprotective effects afforded by sodium–glucose cotransporter 2 (SGLT2) inhibitors, whether the modulation of glucose handling acutely affects sympathetic regulation of arterial pressure remains to be elucidated. In Goto–Kakizaki diabetic rats, we estimated the open-loop static characteristics of the carotid sinus baroreflex together with urine glucose excretion using repeated 11-min step input sequences. After the completion of the 2nd sequence, an SGLT2 inhibitor empagliflozin (10 mg kg−1) or vehicle solution was administered intravenously (n = 7 rats each). Empagliflozin did not significantly affect the baroreflex neural or peripheral arc, despite significantly increasing urine glucose excretion (from 0.365 ± 0.216 to 8.514 ± 0.864 mg·min−1·kg−1, P < 0.001) in the 7th and 8th sequences. The possible sympathoinhibitory effect of empagliflozin may be an indirect effect associated with chronic improvements in renal energy status and general disease conditions.
Aims To quantify in vivo the effects of the soluble guanylate cyclase (sGC) stimulator, vericiguat, on autonomic cardiovascular regulation in comparison with the nitric oxide (NO) donor, sodium nitroprusside. Methods In anesthetized Wistar–Kyoto rats, baroreflex-mediated changes in sympathetic nerve activity (SNA), arterial pressure (AP), central venous pressure (CVP), and aortic flow (AoF) were examined before and during the intravenous continuous administration (10 μg·kg−1·min−1) of vericiguat or sodium nitroprusside (n = 8 each). Systemic vascular resistance (SVR) was calculated as SVR = (AP–CVP) / AoF. Results Neither vericiguat nor sodium nitroprusside affected fitted parameters of the baroreflex-mediated SNA response. Both vericiguat and sodium nitroprusside decreased the AP mainly through their peripheral effects. Vericiguat halved the slope of the SNA–SVR relationship from 0.012 ± 0.002 to 0.006 ± 0.002 mmHg·min·mL−1·%−1 (P = 0.008), whereas sodium nitroprusside caused a near parallel downward shift in the SNA–SVR relationship with a reduction of the SVR intercept from 1.235 ± 0.187 to 0.851 ± 0.123 mmHg·min/mL (P = 0.008). Conclusion Neither vericiguat nor sodium nitroprusside significantly affected the baroreflex-mediated SNA response. The vasodilative effect of vericiguat became greater toward high levels of SNA and AP, possibly reflecting the increased sGC sensitivity to endogenous NO. By contrast, the effect of sodium nitroprusside was more uniform over the range of SNA. These results help better understand cardiovascular effects of vericiguat.
Background: Recently, we developed a novel method for the assessment of very short-term blood pressure lability (BLI). BLI is calculated from the integrated area of blood pressure (BP) power spectral density from 0.01 Hz to 0.1 Hz. Given that low cardiac function suppresses blood pressure (BP) variation, we investigated how the worsening of cardiac function can be reflected in BLI by using a dog model of heart failure with reduced ejection fraction (HFrEF). Methods: In 6 dogs, chronic heart failure was induced through the use of multiple sequential microembolization via bolus injection of polyester microspheres (90μm) into the left descending or circumflex coronary arteries. We repeated coronary microembolization every two weeks and checked the arterial pressure, left ventricular pressure, and echocardiogram under general anesthesia in every session. BLI was calculated from the continuous BP recording by the catheter placed at ascending aorta before micro-embolization. We examined the changes of cardiac function and BLI, and compared them among the sessions of microembolization. Results: In every dog, the repeated microembolization significantly reduced left ventricular ejection fraction (Baseline: 66±4 vs. HF: 38±6, %, P<0.01) and increased left ventricular end diastolic volume (Baseline: 23±4 vs. HF: 36±4, ml, P<0.01), indicating the worsening of cardiac function and remodeling. Although the mean BP did not change significantly, the BLI were significantly lower in heart failure condition (6±2 times microembolization) compared to baseline (Baseline: 0.7±0.2 vs. HF: 0.4±0.1, mmHg, P<0.05). Conclusions: Our findings demonstrate that the BLI in a HFrEF model dog was lower than that in baseline condition with normal hemodynamics. The BLI showed the potential for the assessment of the cardiac function and hemodynamic severity in HFrEF. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Introduction: The ventricular fibrillation (VF) often occurs in acute heart failure patients with Impella support, percutaneous transvalvular left ventricular assist device. Although Impella can preserve blood pressure in some VF patients, the hemodynamic mechanism of Impella during VF remains unclear. Aim: In this study, we examined the impact of Impella on hemodynamics and cerebral and coronary blood flows in a goat model of VF. We also addressed the optimal blood volume status to maintain the Impella circulation during VF. Methods: In six goats, we inserted Impella CP via the left carotid artery. We simultaneously recorded right (RAP) and left atrial pressure (LAP), central blood pressure at ascending aorta (CBP), and the blood flows of pulmonary artery (PA), left coronary circumflex artery (LCX), and right carotid artery (CA). The VF was induced by direct current. We compared the impact of Impella support level (P0, P4 and P8) on hemodynamics and each blood flow. Under P8-Impella supported VF condition, we withdrew blood continuously and observed the left ventricular (LV) suction point at which a frequent negative LV pressure occurred. Results: As shown in Fig. 1 and 2, Impella maintained hemodynamics flow-dependently, indicating the establishment of acute Fontan circulation. In P8-Impella support, systemic (PA flow), LCX and CA blood flows were preserved by 50.1±27.7, 50.7±12.5 and 67.3±5.6%. from baseline, respectively. The blood volume reduction induced the suction of Impella (Fig. 3) at RAP below 9.9±1.9 mmHg. Conclusions: Impella establishes the acute Fontan circulation and preserves hemodynamics including coronary and cerebral blood flows during VF. The optimal blood volume status should be considered to maintain the Impella operation during VF.
Backgrounds: Recently, the combination of Impella, a percutaneous transvalvular left ventricular assist device, and veno-arterial extracorporeal membrane oxygenation (ECMO) have improved the survival rate of cardiogenic shock by its powerful hemodynamic support effect. Meanwhile, the optimal flow control of those devices remains unclear, especially in biventricular failure (BVF). In this study, we established the mathmatical cardiovasular simulation model, and evaluated how the combination therapy impacts both right (RV) and left (LV) ventricular loading. Methods: We used SimulinkⓇ (Mathworks, Inc.) for the simulation. Both the systemic and pulmonary circulation were modeled by using 5-element resistance-capacitance net-work. Four cardiac chambers were represented by time-varying elastance with unidirectional valves (Fig. 1). In LV dysfunction (LV end-systolic elastace was set at low level: 0.4 mmHg/ml), we compared the changes of right (RAP) and left (LAP) atrial pressure, as the marker of ventricular loading, under various RV function and Impella and ECMO flows. Results: Impella slightly increased RAP and reduced LAP regardless of RV systolic function (Fig. 2). In high pulmonary vascular resistance (PVR), the increase of Impella flow augumented RAP, while Impella could not be up-titrated more than 2.8 L/min due to LV suction (Fig. 3). In BVF with high PVR, ECMO decreased RAP and increased LAP in each Impella flow (Fig. 4). Higher ECMO and Impella flows rendered LV extremely small, induced suction, and increased RV preload and RAP. Conclusion: PVR is the major determinant of stable Impella support without inducing RV loading and LV suction. In BVF with high PVR, ECMO reduced RV loading, while decreased LV filling and induced LV suction by Impella. The preemptive simulation study for an individual patient may help the optimal use of mechanical circulatory support device to maximize RV and LV unloading with improving hemodynamics.
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