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2.
JACC Heart Fail ; 7(3): 192-203, 2019 03.
Article in English | MEDLINE | ID: mdl-30819374

ABSTRACT

Post-menopausal women exhibit an exponential increase in the incidence of heart failure with preserved ejection fraction compared with men of the same age, which indicates a potential role of hormonal changes in subclinical and clinical diastolic dysfunction. This paper reviews the preclinical evidence that demonstrates the involvement of estrogen in many regulatory molecular pathways of cardiac diastolic function and the clinical data that investigates the effect of estrogen on diastolic function in post-menopausal women. Published reports show that estrogen deficiency influences both early diastolic relaxation via calcium homeostasis and the late diastolic compliance associated with cardiac hypertrophy and fibrosis. Because of the high risk of diastolic dysfunction and heart failure with preserved ejection fraction in post-menopausal women and the positive effects of estrogen on preserving cardiac function, further clinical studies are needed to clarify the role of endogenous estrogen or hormone replacement in mitigating the onset and progression of heart failure with preserved ejection fraction in women.


Subject(s)
Calcium/metabolism , Estrogens/metabolism , Heart Failure, Diastolic/metabolism , Hypertrophy, Left Ventricular/metabolism , Myocardium/metabolism , Myocytes, Cardiac/metabolism , Postmenopause/metabolism , Stroke Volume , Apoptosis , Connectin/metabolism , Diastole , Energy Metabolism , Estrogen Replacement Therapy , Female , Fibrosis , Heart Failure/metabolism , Heart Failure/physiopathology , Heart Failure, Diastolic/physiopathology , Humans , Hypertrophy, Left Ventricular/physiopathology , Myocardium/pathology , Oxidative Stress , Protein Isoforms
3.
Transl Neurosci ; 7(1): 12-16, 2016.
Article in English | MEDLINE | ID: mdl-28123816

ABSTRACT

The role of cerebral blood flow (CBF) on a maximal breath-hold (BH) in ultra-elite divers was examined. Divers (n = 7) performed one control BH, and one BH following oral administration of the non-selective cyclooxygenase inhibitor indomethacin (1.2 mg/kg). Arterial blood gases and CBF were measured prior to (baseline), and at BH termination. Compared to control, indomethacin reduced baseline CBF and cerebral delivery of oxygen (CDO2) by about 26% (p < 0.01). Indomethacin reduced maximal BH time from 339 ± 51 to 319 ± 57 seconds (p = 0.04). In both conditions, the CDO2 remained unchanged from baseline to the termination of apnea. At BH termination, arterial oxygen tension was higher following oral administration of indomethacin compared to control (4.05 ± 0.45 vs. 3.44 ± 0.32 kPa). The absolute increase in CBF from baseline to the termination of apnea was lower with indomethacin (p = 0.01). These findings indicate that the impact of CBF on maximal BH time is likely attributable to its influence on cerebral H+ washout, and therefore central chemoreceptive drive to breathe, rather than to CDO2.

4.
J Cereb Blood Flow Metab ; 35(1): 66-73, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25370857

ABSTRACT

The roles of involuntary breathing movements (IBMs) and cerebral oxygen delivery in the tolerance to extreme hypoxemia displayed by elite breath-hold divers are unknown. Cerebral blood flow (CBF), arterial blood gases (ABGs), and cardiorespiratory metrics were measured during maximum dry apneas in elite breath-hold divers (n=17). To isolate the effects of apnea and IBM from the concurrent changes on ABG, end-tidal forcing ('clamp') was then used to replicate an identical temporal pattern of decreasing arterial PO2 (PaO2) and increasing arterial PCO2 (PaCO2) while breathing. End-apnea PaO2 ranged from 23 to 37 mm Hg (30 ± 7 mm Hg). Elevation in mean arterial pressure was greater during apnea than during clamp reaching +54 ± 24% versus 34 ± 26%, respectively; however, CBF increased similarly between apnea and clamp (93.6 ± 28% and 83.4 ± 38%, respectively). This latter observation indicates that during the overall apnea period IBM per se do not augment CBF and that the brain remains sufficiently protected against hypertension. Termination of apnea was not determined by reduced cerebral oxygen delivery; despite 40% to 50% reductions in arterial oxygen content, oxygen delivery was maintained by commensurately increased CBF.


Subject(s)
Brain/blood supply , Breath Holding , Cerebrovascular Circulation/physiology , Diving/physiology , Oxygen Consumption/physiology , Adult , Apnea/blood , Apnea/physiopathology , Blood Flow Velocity/physiology , Blood Gas Analysis , Blood Pressure/physiology , Brain/metabolism , Female , Humans , Male , Middle Aged , Oxygen/blood , Respiratory Mechanics/physiology , Young Adult
5.
Am J Physiol Regul Integr Comp Physiol ; 303(11): R1157-64, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23054172

ABSTRACT

Premature ventricular contractions (PVC) elicit larger bursts of multiunit muscle sympathetic nerve activity (MSNA), reflecting the ability to increase postganglionic axonal recruitment. We tested the hypothesis that chronic heart failure (CHF) limits the ability to recruit postganglionic sympathetic neurons as a response to PVC due to the excessive sympathetic activation in these patients. Sympathetic neurograms of sufficient signal-to-noise ratio were obtained from six CHF patients and from six similarly aged control individuals. Action potentials (APs) were extracted from the multiunit sympathetic neurograms during sinus rhythm bursts and during the post-PVC bursts. These APs were classified on the basis of the frequency per second, the content per burst, and the peak-to-peak amplitude, which formed the basis of binning the APs into active clusters. Compared with controls, CHF had higher APs per burst and higher number of active clusters per sinus rhythm burst (P < 0.05). Compared with sinus rhythm bursts, both groups increased AP frequency and the number of active clusters in the post-PVC burst (P < 0.05). However, compared with controls, the increase in burst integral, AP frequency, and APs per burst during the post-PVC burst was less in CHF patients. Nonetheless, the PVC-induced increase in active clusters per burst was similar between the groups. Thus, these CHF patients retained the ability to recruit larger APs but had a diminished ability to increase overall AP content.


Subject(s)
Heart Failure/physiopathology , Neurons/physiology , Sympathetic Nervous System/physiology , Ventricular Premature Complexes/physiopathology , Action Potentials/physiology , Adult , Aged , Axons/physiology , Case-Control Studies , Female , Humans , Male , Middle Aged , Sympathetic Nervous System/cytology , Young Adult
6.
Auton Neurosci ; 169(2): 95-101, 2012 Aug 16.
Article in English | MEDLINE | ID: mdl-22682754

ABSTRACT

The purpose of this study was to assess the differences in cardiac autonomic modulation during maximal static (SA) and dynamic (DA) underwater apneas. Arterial oxygen saturation (SpO(2)), heart rate (HR) and HR variability (SD1 from Poincaré plot and short-term fractal-like scaling exponent, α(1)) were analyzed at the immersed baseline (3 min) and initial, mid- and end-phases (each 30s) of SA and DA in nine elite breath-hold divers. DA and SA lasted 78 ± 8 and 225 ± 20s (mean ± SEM), respectively, and resulted in similar decrements in end-stage SpO(2) (78 ± 3 and 75 ± 3%, p=0.352). During DA, initial increase in HR (from 80 ± 5 to 122 ± 5 bpm, p<0.001) was followed by gradual decrease towards the baseline at mid-apnea and end-apnea phase (101 ± 6 and 80 ± 8 bpm, respectively). During SA, HR decreased at mid-apnea (from 78 ± 4 to 66 ± 3 bpm, p=0.004) but did not decrease further at end-apnea phase (66 ± 4b pm). Decreased SD1 was observed at the initial phase of DA (from 28 ± 5 to 10 ± 4 ms, p=0.005) being lower compared with SA (24 ± 4 ms, p=0.005). At the end of DA and SA, SD1 tended to increase above the baseline (62 ± 16 and 66 ± 10 ms, p=0.128 and p=0.093, respectively, p=0.602 DA vs. SA). α(1) tended to be higher at the end of DA compared with SA (1.17 ± 0.10 vs. 0.79 ± 0.10, p=0.059). We concluded that apnea blunts the effects of exercise on cardiac vagal activity at the end of DA. However, higher HR during DA compared with SA indicates larger cardiac sympathetic activity during DA, as suggested also by slightly higher α(1).


Subject(s)
Apnea/physiopathology , Diving/physiology , Heart Rate/physiology , Heart/physiology , Adult , Apnea/blood , Autonomic Nervous System/physiology , Blood Pressure/physiology , Exercise/physiology , Female , Humans , Male , Oxygen/metabolism , Pulmonary Gas Exchange/physiology , Time Factors
7.
Respir Physiol Neurobiol ; 181(2): 228-33, 2012 Apr 30.
Article in English | MEDLINE | ID: mdl-22465545

ABSTRACT

The growing urge to breathe that occurs during breath-holding results in development of involuntary breathing movements (IBMs). The present study determined whether IBMs are initiated at critical levels of hypercapnia and/or hypoxia during maximal apnoea. Arterial blood gasses at the onset of IBM were monitored during maximal voluntary breath-holds. Eleven healthy men performed breath holds after breathing air, hyperoxic-normocapnia, hypoxic-normocapnia, and normoxic-hypercapnia. Pre-breathing of the gas mixtures facilitated the IBM onset, reducing the time-to-onset for ∼46% (hyperoxic condition) and for ∼80% (hypoxic condition) compared to the normoxic air breathing time. A strong correlation (R=0.83, P=0.002) between arterial partial pressure of CO2 (PaCO2) at IBM onset after pre-breathing hyperoxic and hypercapnic gas mixtures was observed, suggesting the existence of a possible IBM PaCO2 threshold level of ∼6.5 ± 0.5 kPa. No clear "threshold" was observed for partial pressure of arterial O2(PaO2). However, we observed that IBM onset was influenced, in part, by an interaction between PaO2 and PaCO2 levels during maximal apnoea. This study demonstrated the complex interaction between arterial blood-gases and the physiological response to maximal breath holding.


Subject(s)
Apnea/physiopathology , Carbon Dioxide/physiology , Oxygen/physiology , Respiration , Adult , Air , Apnea/blood , Carbon Dioxide/administration & dosage , Carbon Dioxide/blood , Humans , Male , Oxygen/administration & dosage , Oxygen/blood , Partial Pressure , Young Adult
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