Experimental physiology
-
Experimental physiology · Jan 2020
Effects of the menstrual and oral contraceptive cycle phases on microvascular reperfusion.
What is the central question of this study? What are the effects of the menstrual (early follicular and mid-luteal) or monophasic oral contraceptive (inactive- and active-pill) cycle phases on vascular reperfusion of lower limb microvasculature in healthy, active women using the near-infrared spectroscopy (NIRS) vascular occlusion test (VOT) technique? What is the main finding and its importance? We demonstrated that vascular responsiveness in the lower limb microvasculature remained unchanged between the early follicular and mid-luteal phases of the menstrual cycle and inactive- and active-pill phases of the oral contraceptive cycle. These data support that controlling for the cycle phases, within the specific times evaluated in this study, might not be necessary when assessing NIRS-VOT reperfusion rates. ⋯ The objective was to examine whether the menstrual or monophasic oral contraceptive cycle phases affect microvascular responsiveness of the lower limb in healthy, active women. During the follicular or inactive-pill phase and the luteal or active-pill phase of the menstrual or oral contraceptive cycle, respectively, 15 non-oral contraceptive users (mean ± SD; 27 ± 6 years of age) and 15 monophasic oral contraceptive users (24 ± 4 years of age) underwent a lower-limb vascular occlusion test (5 min baseline, 5 min occlusion and 8 min post cuff release). Menstrual cycle phases were verified using an ovulation test. Vascular responsiveness was assessed by calculating the near-infrared spectroscopy-derived muscle oxygen saturation (StO2 ) reperfusion slope (slope 2 StO2 ) and the post occlusion StO2 area under the curve (StO2AUC ) of the tibialis anterior muscle. There were no differences in the reperfusion slope (as a percentage per second; follicular, 1.18 ± 0.48; luteal, 1.05 ± 0.48, inactive-pill, 0.95 ± 0.23; and active-pill, 0.87 ± 0.36; P = 0.09) and area under the curve (as a product of the percentage and seconds; follicular, 1067 ± 562; luteal, 918 ± 414, inactive-pill, 945 ± 702; and active-pill, 750 ± 519; P = 0.09) between the phases of the menstrual or oral contraceptive cycle, regardless of pill generation. The duration of oral contraceptive use was not associated with changes in slope 2 StO2 (r = 0.02, P = 0.94) or StO2AUC (r = -0.34, P = 0.22) between cycle phases. In conclusion, vascular responsiveness remained unchanged between the early follicular and mid-luteal phases of the menstrual cycle and the inactive-pill and active-pill phases of the oral contraceptive cycle.
-
Experimental physiology · Jan 2020
Microvascular blood flow during vascular occlusion tests assessed by diffuse correlation spectroscopy.
What is the central question of this study? What are the characteristics of the time courses of blood flow in the brachial artery and microvascular beds of the skin and skeletal muscle following transient ischaemia? What is the main finding and its importance? Skeletal muscle blood flow was significantly slower than the transient increase in the cutaneous tissue, suggesting mechanistic differences between cutaneous and muscular blood flow distribution after transient ischaemia. These results challenge the use of the cutaneous circulation as globally representative of vascular function. ⋯ Vascular function can be assessed by measuring post-occlusion hyperaemic responses along the arterial tree (vascular occlusion test; VOT). It is currently unclear if responses are similar across vascular beds following cuff release, given potential differences in compliance. To examine this, we compared laser Doppler-derived blood flux in the cutaneous circulation (LDFcut ) and skeletal muscle microvascular blood flux (BFI) using diffuse correlation spectroscopy (DCS), to brachial artery blood flow (BABF) during VOT. We hypothesized that during a VOT following cuff release, (1) BFI response would be delayed compared to the brachial artery response, and (2) time to peak blood flux in the cutaneous vasculature would be slower than both brachial artery and skeletal muscle responses. Seven healthy men (26 ± 4 years) performed three trials of a brachial artery VOT protocol with 10 min of rest between trials. A combined DCS and near-infrared spectroscopy probe provided BFI and oxygenation characteristics (total-[haem]), respectively, of skeletal muscle. BABF was determined via Doppler ultrasound and microvascular cutaneous blood flux was determined via LDFcut . Following cuff release, time to peak of BFI (32.3 ± 6.0 s) was significantly longer than BABF (7.3 ± 2.5 s), LDFcut (10.0 ± 6.4 s) and total-[haem] (14.2 ± 8.3 s) (all P < 0.001). However, time to peak of BABF, LDFcut and total-[haem] were not significantly different (P > 0.05). These results suggest mechanistic differences in control of cutaneous and muscular blood flow distribution after transient ischaemia.
-
Experimental physiology · Nov 2019
Tacrolimus restores the high- and low-pressure baroreflex control of renal sympathetic nerve activity in cisplatin-induced renal injury rats.
What is the central question of this study? Does immunosuppression restore the baroreflex control of renal sympathetic nerve activity (RSNA) in an animal model of kidney injury? What is the main finding and its importance? Tacrolimus, a calcineurin inhibitor, restored the high- and low-pressure baroreflex control of RSNA following cisplatin-induced renal injury. ⋯ Cisplatin administration causes depression of renal haemodynamic and excretory function and is associated with renal sympatho-excitation and loss of baroreflex regulation of renal sympathetic nerve activity (RSNA). This study investigated whether administration of the immunosuppressant tacrolimus in this cisplatin-mediated renal injury model could restore, or the acute intra-renal infusion of tumour necrosis factor α (TNF-α) could blunt, the high- or low-pressure baroreflex control of RSNA. Groups of control and cisplatin-treated (5 mg kg-1 , i.p. on day 0) rats received either saline or tacrolimus (0.25 mg kg-1 day-1 , i.p.) for 7 days prior to study. Rats were anaesthetised and prepared for measurement of mean arterial pressure (MAP), heart rate (HR) and RSNA. Baroreflex gain curves were generated and the degree of renal sympatho-inhibition determined (area under the curve (AUC) reported as %RSNA min) during acute volume expansion. Intrarenal TNF-α infusion (0.3 µg kg-1 h-1 ) in control rats decreased baroreflex gain by 32% (P < 0.05) compared to intra-renal saline infusion. In the cisplatin group (MAP: 98 ± 14 mmHg; HR: 391 ± 24beats min-1 ), the baroreflex gain for RSNA was 39% (P < 0.05) lower than that for the control group (MAP: 91 ± 7 mmHg; HR: 382 ± 29 beats min-1 ). In cisplatin-treated rats given daily tacrolimus (MAP: 84 ± 12 mmHg; HR: 357 ± 30 beats min-1 ), the baroreflex gain and renal sympatho-inhibition (AUC, 2440 ± 1071 vs. 635 ± 498% min) were restored to normal values. These findings provide evidence for the view that cisplatin administration initiates an injury involving inflammation which may contribute to the deranged baroreflex regulation of RSNA. This phenomenon appears mediated in part via the renal innervation.
-
Experimental physiology · Nov 2019
Effect of flunarizine on defibrillation outcomes and early refibrillation in a canine model of prolonged ventricular fibrillation.
What is the central question of this study? Can successful electrical shock in combination with a delayed after-depolarization (DAD) blocker suppress early refibrillation episodes following long duration ventricular fibrillation (LDVF)? What is the main finding and its importance? Flunarizine significantly reduced the activation of LDVF and early ventricular fibrillation (VF) recurrence following LDVF, suggesting that DADs potentially contribute to refibrillation in prolonged VF. Thus, DAD inhibition can be used as an adjunctive therapy for electrical defibrillation to treat prolonged VF and suppress refibrillation following LDVF. ⋯ This study attempts to detect changes in the defibrillation threshold (DFT) at different stages of ventricular fibrillation (VF) (short duration VF, SDVF; long duration VF, LDVF) and during early refibrillation following successful defibrillation of LDVF by giving flunarizine, a blocker of delayed after-depolarizations (DADs). Twelve beagles were divided into two groups (the control group, n = 6; and the flunarizine group, n = 6). Two 64-electrode basket catheters were deployed into the left and the right ventricles for global endocardium mapping. The DFTs of SDVF and LDVF were determined at 20 s and 7 min, respectively, after VF induction in each group. Any refibrillation episodes were recorded within 15 min after the first successful defibrillation of LDVF. In the flunarizine group, the SDVF-DFT values before and after the drug were not significantly different. The 7 min LDVF-DFTs were markedly reduced by 26% (P < 0.05, the control group) and 38% (P < 0.01, the flunarizine group) compared to the 20 s SDVF-DFTs within each group. The difference between SDVF-DFT and LDVF-DFT after flunarizine was larger than that in the control group (213 ± 65 vs. 120 ± 84 V, P < 0.05). The number of refibrillation episodes per animal (1.3 ± 1.0) following successful defibrillation of LDVF after flunarizine was 48% of that in controls (2.7 ± 2.0, P < 0.05). The effect of flunarizine on SDVF-DFT and LDVF-DFT indicates that the role of DADs in the defibrillation mechanism may differ as VF continues. Flunarizine significantly reduced early VF recurrence following LDVF, suggesting that DADs potentially contribute to refibrillation in a canine model of prolonged VF.
-
Experimental physiology · Jun 2019
Reduced insulin sensitivity in young, normoglycaemic subjects alters microvascular tissue oxygenation during postocclusive reactive hyperaemia.
What is the central question of the study? Are measures of reduced insulin sensitivity in young, normoglycaemic subjects correlated with near-infrared spectroscopy-derived microvascular responsiveness [tissue oxygen saturation reperfusion rate (STO2 upslope)] during postocclusive reactive hyperaemia? What is the main finding and its importance? A sevenfold range of hepatic insulin sensitivity is significantly correlated (r = 0.44, P = 0.02) with STO2 upslope after transient tissue ischaemia. Near-infrared spectroscopy may be an important tool for determining altered microvascular function before onset of hyperglycaemia. Identification of pre-type 2 diabetes much earlier than with the present clinical criteria is important for pre-emptive measures against microvascular deterioration. ⋯ Near-infrared spectroscopy (NIRS) measurement of postocclusive reactive hyperaemia (PORH) tissue oxygen saturation reperfusion rate [STO2 upslope (as a percentage per minute)] has recently been correlated with the percentage of flow-mediated dilatation (%FMD). Cardiovascular disease is associated with impairments in %FMD. Reduced insulin sensitivity may negatively affect the vascular system for many years before prediabetes/type 2 diabetes states. The aim of this study was to determine whether static and dynamic STO2 parameters during PORH are correlated with reduced insulin sensitivity in young, normoglycaemic subjects. Glucose and insulin were measured during an oral glucose tolerance test in 18- to 26-year-old, healthy subjects (11 men and 11 women), and STO2 was measured during PORH of antebrachial muscle. Hepatic (ISIHOMA ) and whole-body (ISICOMP ) insulin sensitivities were calculated. The STO2 upslope was negatively correlated with minimal STO2 (r = -0.5, P = 0.01). The change of STO2 from minimum to baseline (ΔSTO2 ) was significantly negatively correlated with fasting insulin (r = -0.5, P = 0.01) and a positively correlated with ISIHOMA (r = 0.65, P = 0.001). The minimum STO2 was significantly negatively correlated with ISIHOMA , and STO2 upslope was significantly positively correlated with ISIHOMA (r = 0.44, P = 0.02). The minimum STO2 (a measure of O2 extraction while the cuff was inflated), ΔSTO2 (a measure of the amount of reperfusion) and STO2 upslope (a measure of responsiveness of the microcirculation to ischaemia) were all positively correlated with ISIHOMA , one of the longest-used measures of insulin sensitivity. The NIRS-derived STO2 might be a useful tool for assessing how levels of reduced insulin sensitivity in young, normoglycaemic adults affect the microvasculature.