We examined urine excretion during primary acute sympathetic activation (PASA) in anesthetized Wistar-Kyoto rats. Since arterial pressure (AP) changes with sympathetic nerve activity (SNA) during PASA, urine excretion reflects a neurally-mediated antidiuretic effect combined with an effect of pressure diuresis. We hypothesized that preventing AP changes under PASA would enable the direct estimation of the neurally-mediated antidiuretic effect alone. We changed the isolated carotid sinus pressure stepwise from 60 to 180 mmHg and compared the relationship of normalized urine flow (nUF, urine flow normalized by body weight) versus SNA between conditions allowing and preventing baroreflex-mediated changes in the mean AP. The slope of the SNA-nUF relationship was nUFvar = 0.444 ± 0.074 μL·min−1·kg−1·%−1 when the mean AP was variable, whereas it was nUFfix = −0.143 ± 0.032 μL·min−1·kg−1·%−1 when the mean AP was fixed at 100 mmHg (n = 7 rats). The slope associated with the effect of pressure diuresis alone, calculated as nUFvar − nUFfix, was 0.586 ± 0.105 μL·min−1·kg−1·%−1. Hence, the potency of the neurally-mediated antidiuretic effect, | nUFfix| / ( nUFvar − nUFfix), was 0.235 ± 0.014 relative to the effect of pressure diuresis under PASA. Our findings would aid an integrative understanding of the effects of renal hemodynamic and sympathetic modulations on urine output function.
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.
Chymase is a protease stored in mast cell granules that produces angiotensin II (ANG II) from angiotensin I (ANG I) and is associated with tissue injury, inflammation, and remodeling, especially involving the cardiovascular system. As cardiovascular events occur, chymase is activated by degranulation to the extracellular matrix. Although chymase has been suggested to be associated with cardiovascular disease progression, there are not enough reports in veterinary medicine. Patent ductus arteriosus (PDA) is a common congenital cardiac disease in veterinary medicine. Almost all cases of PDA can be treated surgically to prevent the development of congestive heart disease and/or pulmonary hypertension. The aims of the present study were to measure chymase activity before and after PDA occlusions, and to investigate the relationships between the congestive and hemodynamic states of PDA and chymase activity. In the present study, 17 puppies diagnosed with PDA were included and all puppies completely recovered to the level of healthy dogs. Chymase activity significantly decreased at 2 months after the operation, along with the echocardiography parameters of congestion. Therefore, plasma chymase activity may be useful as a novel predictor for understanding the hemodynamics of PDA in veterinary medicine.
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.
Background Rapid reduction of heart rate (HR) is the most evident physiological response of vagal nerve stimulation (VNS). Since HR reduction is the most potent factor to decrease myocardial oxygen consumption rate (MVO2), the appropriate VNS can exert cardio-protective effects. It is also known that VNS reduces inflammation, oxidative stress, and sympathetic overload. In addition, the VNS during ischemia-reperfusion is known to attenuate myocardial damage by studies in various animal species. Despite the presence of preclinical evidence of VNS benefits, the lack of the device has limited the translation of this technology to clinical practice. We have recently developed an intravenous VNS catheter (JOHAKU, Neuroceuticals Inc.) that can stimulate the right vagal nerve via superior vena cava (SVC) (Figure 1) on temporary basis. Purpose We aimed to confirm the feasibility of JOHAKU as a device to modulate heart rate and MVO2 rapidly by a canine experiment. Methods In eight beagle dogs, JOHAKU was inserted from the right femoral vein and placed at the SVC level. The stimulation intensity was adjusted to 10–20 V (20 Hz). We simultaneously recorded electrocardiogram and intraarterial blood pressure (BP). In three of eight dogs, we measured the left anterior descending coronary artery flow and oxygen saturations of arterial and coronary sinus blood to calculate MVO2. We compared HR, BP, and MVO2 during JOHAKU stimulation to ones at baseline. Results As shown in Figure 2, JOHAKU attenuated HR immediately after stimulation. Compared with baseline, JOHAKU significantly reduced HR (baseline: 135±13 vs. 5 min on stimulation: 107±13 bpm, p<0.05), and did not affect mean BP significantly (96.2±22.8 vs. 89.4±26.6 mmHg, P=0.59). HR promptly recovered to baseline level after JOHAKU stopped. JOHAKU also reduced MVO2 (0.57±0.43 vs. 0.48±0.38 ml/min, p<0.05). Conclusion JOHAKU rapidly attenuated cardiac metabolism burden via the rapid HR reduction. The controllability of HR by JOHAKU without affecting BP enables us to apply the VNS even for patients with hemodynamic instability, such as heart failure and acute myocardial infarction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical and Research Development
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