Carotid Baroreceptor Magnetic Activation and Beat-to-Beat Blood Pressure Variability, Implications to Treat Abrupt Blood Pressure Elevation in Labile Hypertension.

Mounting evidence suggests enhanced blood pressure (BP) variability (BPV) independent role in cardiovascular (CV) damage. The goal was to estimate the effect of the carotid baroreceptor (CB) magnetic stimulation on sudden high BP elevation. Mean femoral arterial BP (MAP), heart rate (HR), baroreflex sensitivity (BRS), and ear lobe skin microcirculatory blood flow, by microphotoelectric plethysmography (MPPG), were simultaneously recorded in conscious rabbits sedated by pentobarbital intravenous (i.v.) infusion (5 mg/kg/h) after 40 min CB exposure to 350 mT static magnetic field (SMF), by Nd2 -Fe14 -B magnets (n = 14), or sham magnets exposure (n = 14). BRS was assessed from HR and MAP responses to abrupt hypotension induced by i.v. bolus injections of nitroprusside (Ni) and abrupt MAP elevation (MAPAE ) by i.v. bolus of phenylephrine (Ph). Beat-to-beat BPV was estimated by MAP standard deviation. SMF CB exposure significantly increased BRSNi (74.5 ± 17.8%, P < 0.001) and microcirculation (23.8% ± 11.0%, P = 0.039); decreased MAP (-5.7 ± 1.7%, P < 0.014) and phenylephrine-induced MAPAE (-19.1%, P = 0.043). MAPAE positively correlated with resting MAP (r = 0.342, P = 0.0383) and MAP SD (r = 0.383, P = 0.0194), and inversely with BRSPh (r = -0.47, P = 0.0156). SMF CB exposure enhanced the nitroprusside, which acts by releasing nitric oxide (NO), vasodilatory effect. This indicates arterial baroreflex to improve vessel sensitivity to NO, which is a new physiology with BP buffering effect. A positive correlation of MAP SD to phenylephrine BP ramps suggests a causal relationship and BPV prognostic significance to forecast abrupt BP elevation. Mechano/baroreceptor magneto-sensing property proposed to be the basic physiology by which SMFs boost CV autonomic regulation with potential implementation in high CV risk labile arterial hypertensive disease. © 2022 Bioelectromagnetics Society.

Static Magnetic Field Versus Systemic Calcium Channel Blockade Effect on Microcirculation: Possible Mechanisms and Clinical Implementation.

The goal was to compare static magnetic field (SMF, generated by Nd2 -Fe14 -B magnets) vasodilator capacity with verapamil (VER, a potent, clinically verified Ca2+ channel-blocking agent), aimed to assess SMF implementation in conditions with vascular ischemia. Skin microcirculatory blood flow measured by microphotoelectric plethysmogram was recorded in conscious rabbits after 40 min of 0.25 T SMF regional exposure to ear microvascular net (SMF-Vas, n = 20), or 0.35 T to carotid baroreceptors (SMF-Car, n = 14), and compared with that after 30 min VER intravenous infusion (20 µg/kg/min, n = 20). The principal finding is that SMF-Vas, SMF-Car, and VER significantly increased microcirculatory blood flow by 17.9 ± 9.58%, 22.6 ± 11.11%, and 30.5 ± 14.06% (mean ± SEM) respectively, and there was no significant difference between all three treatments (P = 0.986). Microvascular dilation was accompanied by significant decrease of blood pressure in VER and SMF-Car cases. The decrease of arterial baroreflex sensitivity in VER contrasted with its increase in SMF-Car, coupled with improved vessel sensitivity to nitric oxide (NO) dilatory effect. This suggests that SMF can have a strong vasodilator property tailored to address diabetic, mainly NO-deficient, neural, and myogenic microvascular dysfunction, especially employing both SMFs' vasodilation synergy. Bioelectromagnetics. 2020;41:447-457. © 2020 Bioelectromagnetics Society.

Baroreceptor stimulation enhanced nitric oxide vasodilator responsiveness, a new aspect of baroreflex physiology.

OBJECTIVE: Increasing evidence suggests that endothelial nitric oxide (NO) deficit and baroreflex dysfunction are associated with a variety of cardiovascular conditions, ranging from arterial hypertension to stroke and coronary heart disease, importantly appearing even in preclinical stages of the disease. To test the hypothesis that the arterial baroreflex has a modulatory effect on NO-dependent vasodilation, sodium nitroprusside (SNP), a spontaneous NO-donor, vasodilatory effect was studied in conjunction with sinocarotid baroreceptor magnetic stimulation and potential implementation in NO deficiency states. METHODS: Mean femoral artery blood pressure (MAP), heart rate (HR) and ear lobe skin microcirculatory blood flow, measured by a microphotoelectric plethysmogram (MPPG), were simultaneously recorded in conscious rabbits before and after 40-min sinocarotid baroreceptor exposure to 350 mT static magnetic field (SMF), generated by Nd2-Fe4-B alloy (n=8) or sham magnets (n=8, controls). Arterial baroreflex sensitivity (BRS) was measured by changes in HR and MAP (ΔHR/ΔMAP) after intravenous bolus injections of SNP and phenylephrine. RESULTS: The vasodilatory effect of SNP significantly increased after SMF sinocarotid baroreceptor exposure (MPPGbeforeSMF: 2.57 ± 0.81 V vs. MPPGafterSMF: 7.82 ± 1.61 V, p<0.0001) and positively correlated with significant increase in BRS (r=0.51, p=0.01). CONCLUSIONS: Baroreflex-mediated increment in vessel sensitivity to NO is suggested to be a new mechanism in baroreflex physiology with potential implementation in cardiovascular conditions where NO deficit and autonomic dysfunction increase the risk of morbidity and mortality substantially.

Static magnetic field effect on microcirculation, direct versus baroreflex-mediated approach.

We compared in conscious rabbits, sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg(- 1) h(- 1)), the effect of a static magnetic field (SMF), generated by Nd2-Fe14-B magnets, on microcirculation during its 40 min local exposure to the microvascular network in cutaneous tissue [20 sham exposure and 20 SMF (0.25 T) exposure runs] or to sinocarotid baroreceptors [14 sham exposure and 14 SMF (0.35 T) exposure runs]. Mean femoral artery blood pressure (BP), heart rate (HR), arterial baroreflex sensitivity (BRS), assessed from HR and BP responses to i.v. bolus of nitroprusside and phenylephrine, and microcirculatory blood flow, using microphotoelectric plethysmography (MPPG), were simultaneously monitored. SMF significantly increased microcirculation on a 17.8% in microvascular and on a 23.3% in baroreceptor exposure series. In baroreceptor exposure series, SMF significantly decreased BP, increased heart rate variability, BRS and sodium nitroprusside (NO-donor) i.v. bolus microcirculatory vasodilatory effect. These suggest augmentation of the arterial baroreflex capacity support NO-dependent vasodilation, by increased sensitivity of vessels to NO, to be a new physiological mechanism of BP buffering and microcirculatory control. A significant positive correlation was also found between increase in BRS and in MPPG (r = 0.66, p < 0.009), indicating baroreflex participation in the regulation of the microcirculation and its enhancement after SMF exposure. Both direct and baroreflex-mediated approaches demonstrate SMF significant vasodilatory effect with potential clinical implication in macro- and microcirculatory disorders.

Static magnetic field blood pressure buffering, baroreflex vs. vascular blood pressure control mechanism.

PURPOSE: We compared the effect of static magnetic field (SMF) and verapamil, a potent vascular calcium channel blocking agent, on sudden elevation in blood pressure in conjunction with arterial baroreflex sensitivity (BRS) and microcirculation. MATERIALS AND METHODS: Forty-four experiments were performed on conscious rabbits sedated using pentobarbital intravenous (i.v.) infusion (5 mg kg(-1) h(-1)). Mean femoral artery blood pressure (MAP), heart rate, BRS and ear lobe skin microcirculatory blood flow, estimated using microphotoelectric plethysmography (MPPG), were simultaneously measured after a 40 min exposure of the sinocarotid baroreceptors to 350 mT SMF, generated by Nd(2)-Fe(14)-B magnets, or 30 min of verapamil i.v. administration (20 microg kg(-1) min(-1)). BRS was assessed from heart rate and MAP responses to i.v. bolus of nitroprusside and phenylephrine. RESULTS: The decrease in phenylephrine-induced abrupt elevation in MAP (DeltaMAP(AE)) was significantly larger after verapamil than after SMF exposure. DeltaMAP(AE) inversely correlated with verapamil-induced significant increase in DeltaMPPG (r = 0.53, p < 0.000) and with SMF-induced significant increase in DeltaBRS (r = 0.47, p < 0.016). CONCLUSIONS: Our results suggest that verapamil-potentiated vascular blood pressure buffering mechanism was more effective than SMF-potentiated baroreflex-mediated blood pressure buffering mechanism, and a potential benefit of both approaches in cardiovascular conditions with abrupt high elevation in blood pressure.

Geomagnetic field modulates artificial static magnetic field effect on arterial baroreflex and on microcirculation.

Spreading evidence suggests that geomagnetic field (GMF) modulates artificial magnetic fields biological effect and associated with increased cardiovascular morbidity. To explore the underlying physiological mechanism we studied 350 mT static magnetic field (SMF) effect on arterial baroreflex-mediated skin microcirculatory response in conjunction with actual geomagnetic activity, reflected by K and K ( p ) indices. Fourteen experiments were performed in rabbits sedated by pentobarbital infusion (5 mg/kg/h). Mean femoral artery blood pressure, heart rate, and the ear lobe skin microcirculatory blood flow, measured by microphotoelectric plethysmogram (MPPG), were simultaneously recorded before and after 40 min of NdFeB magnets local exposure to sinocarotid baroreceptors. Arterial baroreflex sensitivity (BRS) was estimated from heart rate/blood pressure response to intravenous bolus injections of nitroprusside and phenylephrine. We found a significant positive correlation between SMF-induced increase in BRS and increment in microvascular blood flow (DeltaBRS with DeltaMPPG, r=0.7, p<0.009) indicated the participation of the arterial baroreflex in the regulation of the microcirculation and its enhancement after SMF exposure. Geomagnetic disturbance, as opposed to SMF, decreased both microcirculation and BRS, and counteracted SMF-induced increment in microcirculatory blood flow (K-index with DeltaMPPG; r (s)=-0.55, p<0.041). GMF probably affected central baroreflex pathways, diminishing SMF direct stimulatory effect on sinocarotid baroreceptors and on baroreflex-mediated vasodilatatory response. The results herein may thus point to arterial baroreflex as a possible physiological mechanism for magnetic-field cardiovascular effect. It seems that geomagnetic disturbance modifies artificial magnetic fields biological effect and should be taken into consideration in the assessment of the final effect.

Static magnetic field effect on the arterial baroreflex-mediated control of microcirculation: implications for cardiovascular effects due to environmental magnetic fields.

Increasing evidence suggests that time-varying and static magnetic fields in the environment might affect the cardiovascular system. To explore the underlying physiology, the effect of static magnetic fields (SMFs) on the carotid baroreflex control of microcirculation was studied. Twenty-four hemodynamic monitorings were performed in rabbits sedated by pentobarbital infusion (5 mg/kg/h) during experiments that lasted 120 min. Mean femoral artery blood pressure, heart rate, and ear lobe skin microcirculatory blood flow, measured by microphotoelectric plethysmogram (MPPG), were simultaneously recorded before and after a 40 min exposure of the sinocarotid baroreceptors to Nd(2)-Fe(14)-B alloy magnets (n = 14) or sham magnets (n = 10, control series). The local SMF field was 350 mT, at the baroreceptors' site. Arterial baroreflex sensitivity (BRS) was estimated from heart rate/blood pressure response to intravenous bolus injections of nitroprusside and phenylephrine. A significant positive correlation was found between the SMF-induced increase in BRS (DeltaBRS = BRS(afterSMF) - BRS(priorSMF)) and the increment in microvascular blood flow (DeltaMPPG = MPPG(afterSMF) - MPPG(priorSMF)) (r = 0.66, p < 0.009). The SMF probably modulated the arterial baroreflex-mediated microcirculatory control. This could represent one possible mechanism how environmental magnetic fields act on the cardiovascular system, and a method how to complexly adjust macro- and microcirculation with potential clinical implementation.

Geomagnetic field effect on cardiovascular regulation.

The goal of the present research was try to explain the physiological mechanism for the influence of the geomagnetic field (GMF) disturbance, reflected by the indices of the geomagnetic activity (K, K(p), A(k), and A(p) indices), on cardiovascular regulation. One hundred forty three experimental runs (one daily) comprising 50 min hemodynamic monitoring sequences were carried out in rabbits sedated by pentobarbital infusion (5 mg/kg/h). We examined the arterial baroreflex effects on the short term blood pressure and heart rate (HR) variabilities reflected by the standard deviation (SD) of the average values of the mean femoral arterial blood pressure (MAP) and the HR. Baroreflex sensitivity (BRS) was estimated from blood pressure/HR response to intravenous (i.v.) bolus injections of vasoconstrictor (phenylephrine) and vasodilator (nitroprusside) drugs. We found a significant negative correlation of increasing GMF disturbance (K(p)) with BRS (P = 0.008), HR SD (P =0.022), and MAP SD (P = 0.002) signifying the involvement of the arterial baroreflex mechanism. The abrupt change in geomagnetic disturbance from low (K = 0) to high (K = 4-5) values was associated with a significant increase in MAP (83 +/- 5 vs. 99 +/- 5 mm Hg, P = 0.045) and myocardial oxygen consumption, measured by MAP and HR product (24100 +/- 1800 vs. 31000 +/- 2500 mm Hg. bpm, P = 0.034), comprising an additional cardiovascular risk. Most likely, GMF affects brainstem and higher neural cardiovascular regulatory centers modulating blood pressure and HR variabilities associated with the arterial baroreflex.

Artificial static and geomagnetic field interrelated impact on cardiovascular regulation.

Spreading evidence suggests that environmental and artificial magnetic fields have a significant impact on cardiovascular system. The modulation of cardiovascular regulatory mechanisms may play a key role in observed effects. The objective was to study interrelated impacts of artificial static magnetic field (SMF) and natural geomagnetic field (GMF) on arterial baroreceptors. We studied baroreflex sensitivity (BRS) in conscious rabbits before and after 40 min of sham (n = 20) or application of Nd2-Fe14-B alloy magnets (n = 26) to the sinocarotid baroreceptor region in conjunction with GMF disturbance during the actual experiment, determined by K- and A(k)-indexes from a local geomagnetic observatory. SMF at the position of baroreceptors was 0.35 T. BRS was estimated from peak responses of mean arterial pressure (MAP) and heart rate expressed as percentages of the resting values preceding each pair of pressure (phenylephrine) and depressor drug (nitroprusside) injections. We observed a significant increase in BRS for the nitroprusside depressor test (0.78 +/- 0.1 vs. 1.15 +/- 0.14 bpm/mmHg%, initial value vs. SMF exposure, P <.0002) and a tendency for phenylephrine pressor test to increase in BRS. Prior to SMF exposure, a significant positive correlation was found between actual K index values and MAP (t = 2.33, P =.025, n = 46) and a negative correlation of the K index with BRS (t = -3.6, P =.001, n = 46). After SMF exposure we observed attenuation of the geomagnetic disturbance induced a decrease in BRS. Clinical trials should be performed to support these results, but there is a strong expectation that 0.35 T SMF local exposure to sinocarotid baroreceptors will be effective in cardiovascular conditions with arterial hypertension and decreased BRS, due to a favorable SMF effect on the arterial baroreflex. Magnets to the sinocarotid triangle along with modification of the pharmacotherapy for hypertension should be especially effective on days with intense geomagnetic disturbance, in moderating sympathetic activation and baroreceptor dysfunction.

Verapamil protective effect on natural and artificial magnetic field cardiovascular impact.

Previously we found an opposite effect of artificial static magnetic field (SMF) and natural geomagnetic field (GMF) on arterial baroreceptors. A 0.35 T SMF increased baroreflex sensitivity (BRS), whereas GMF disturbance decreased BRS. Here, we investigated interrelated impacts on arterial baroreceptors of 0.35 T SMF, generated by Nd(2)-Fe(14)-B alloy magnets, GMF, and verapamil, a Ca(2+) channel blocking agent. We measured BRS in rabbits before and after local SMF exposure of sinocarotid baroreceptors or after simultaneous SMF and verapamil application, in conjunction with geomagnetic disturbance during actual experimental run (determined by K-index) and geomagnetic disturbance over the preceding 24 h of each experiment (A(k)-index). BRS was estimated from peak responses of mean arterial pressure (MAP) and heart rate, expressed as percentages of the resting values preceding each pair of pressure (phenylephrine) and depressor drug (nitroprusside) injections. Prior to verapamil and/or SMF application we found a significant positive correlation of K-index with MAP (t = 2.39, P =.021, n = 44), but negative with BRS (t = -4.60, P =.0003, n = 44), and found a negative correlation of A(k)-index with BRS (t = -2.7, P = 0.01, n = 44). SMF induced an increase in BRS (0.79 +/- 0.1 vs. 1.15 +/- 0.1 bpm%/mmHg%, initial value vs. SMF exposure, P <.0002, n = 26). Verapamil infusion blocked the SMF and GMF effect on BRS, indicating Ca(2+) channels as a possible site of both fields' impact. SMF and GMF probably affect baroreceptor sensory transduction, modulating baroreceptor membranes' Ca(2+) channel permeability.

Effect of 0.25 T static magnetic field on microcirculation in rabbits.

We showed previously in rabbits that 0.2 and 0.35 T static magnetic field (SMF) modulated systemic hemodynamics by arterial baroreceptors. We now have measured the effect of 0.25 T SMF on microcirculation within cutaneous tissue of the rabbit ear lobe by the rabbit ear chamber (REC) method. Forty experimental runs (20 controls and 20 SMF) were carried out in eight different rabbits with an equal number of control and SMF experiments on each individual. Rabbits were sedated by pentobarbital sodium (5 mg/kg/h, i.v.) during the entire 80 min experiment. SMF was generated by four neodium-iron-boron alloy (Nd2-Fe14-B) magnets (15 x 25 x 30 mm, Neomax, PIP - Tokyo Co., Ltd., Tokyo, Japan), positioned around the REC on the observing stage of an optical microscope. The direct intravital microscopic observation of the rabbit's ear microvascular net, along with simultaneous blood flow measurement by microphotoelectric plethysmography (MPPG), were performed PRE (20 min, baseline), DURING (40 min), and POST (20 min) magnetic field exposure. The control experiments were performed under the same conditions and according to the same time course, but without magnetic field. Data were analyzed comparing MPPG values and percent change from baseline in the same series, and between corresponding sections of control and SMF runs. In contrast to control series (100+/-0.0%-90.0+/-5.4%-87.7+/-7.1%, PRE-EXPOSURE-POST), after magnetic field exposure we observed increased blood flow (100+/-0.0%-117.8+/-9.6%*-113.8+/-14.0%, *P<0.05) which gradually decreased after exposure cessation. We propose that long exposure of a high level nonuniform SMF probably modifies microcirculatory homeostasis through modulation of the local release of endothelial neurohumoral and paracrine factors that act directly on the smooth muscle of the vascular wall, presumably by affecting ion channels or second messenger systems.