Peripheral Vascular Mechanisms Research Articles

Noninvasive Monitoring of Simulated Hemorrhage and Whole Blood Resuscitation

Hemorrhage is the leading cause of preventable death from trauma. Accurate monitoring of hemorrhage and resuscitation can significantly reduce mortality and morbidity but remains a challenge due to the low sensitivity of traditional vital signs in detecting blood loss and possible hemorrhagic shock. Vital signs are not reliable early indicators because of physiological mechanisms that compensate for blood loss and thus do not provide an accurate assessment of volume status. As an alternative, machine learning (ML) algorithms that operate on an arterial blood pressure (ABP) waveform have been shown to provide an effective early indicator. However, these ML approaches lack physiological interpretability. In this paper, we evaluate and compare the performance of ML models trained on nine ABP-derived features that provide physiological insight, using a database of 13 human subjects from a lower-body negative pressure (LBNP) model of progressive central hypovolemia and subsequent progressive restoration to normovolemia (i.e., simulated hemorrhage and whole blood resuscitation). Data were acquired at multiple repressurization rates for each subject to simulate varying resuscitation rates, resulting in 52 total LBNP collections. This work is the first to use a single ABP-based algorithm to monitor both simulated hemorrhage and resuscitation. A gradient-boosted regression tree model trained on only the half-rise to dicrotic notch (HRDN) feature achieved a root-mean-square error (RMSE) of 13%, an R2 of 0.82, and area under the receiver operating characteristic curve of 0.97 for detecting decompensation. This single-feature model's performance compares favorably to previously reported results from more-complex black box machine learning models. This model further provides physiological insight because HRDN represents an approximate measure of the delay between the ABP ejected and reflected wave and therefore is an indication of cardiac and peripheral vascular mechanisms that contribute to the compensatory response to blood loss and replacement.

Post-Exercise Hyperthermia Cerebral Blood Flow Hemodynamics Are Similar Between Males And Females

PURPOSE: Females have greater orthostatic intolerance and increased adrenergic sensitivity to passive heat stress compared to males. It is unknown how cerebral blood flow is affected during post-exercise heat stress. We tested the hypothesis that females would have lower middle cerebral artery blood flow velocity (MCAvmean) during post-exercise hyperthermia. METHODS: Twenty-two healthy active adult (7 day activity: 8620±3008 steps/day; VO2max: 49±10 mL/kg/min ) subjects (11M/11F, 22.4±4.9y, 169±7.55cm, 68.3±13kg) exercised at a similar metabolic heat production (M: 7.1±1.5 W/kg and F: 6.9±1.4 W/kg; P=0.32) for 60 minutes (cycle ergometer) in cool (24±0.00C; 14.4±3.6%Rh) and hot (42.3±0.20C; 27.9±5.5%Rh) conditions in random order with a 7 day washout. During 1-hour post-exercise recovery, Transcranial Doppler examined MCAvmean, pulsatility index (PI) and intracranial pressure (ICP). Systemic vascular responses for mean arterial pressure (MAP), augmentation index (Alx), pulse wave velocity (PWV), systemic vascular resistance (SVR), and change in intestinal temperature (ΔTin) and heart rate (ΔHR) and were measured during 1-hour recovery. Area under the curve (AUC) variables were analyzed using a mixed model 2-way repeated-measures analysis of variance for interaction (I) and main effects (ME) for Condition x Sex. Alpha priori was set at P<0.05. RESULTS: Exercise thermal (ΔTin, Cool: Δ0.5±0.10C, Hot: Δ1.5±0.60C; ME: Condition; P<0.0001) and cardiovascular strain (ΔHR Cool: 58±15 b/min, Hot: 71±15 b/min; ME: Condition; P<0.01) was similar between groups that increased in hot compared to cool condition. During recovery both sexes had a similar AUC MCAvmean; however, MCAvmean was lower in hot compared to cool (ME: Condition; P<0.03). Females also showed reduced stiffness (AUC PWV and Alx) compared to males (ME: Condition; P<0.0001; ME: Sex, P<0.0008). Females had greater AUC SVR compared to males in both conditions (ME: sex; P<0.01). There were no differences for MAP, PI, or ICP between the Condition or Sex. CONCLUSIONS: These data suggest that no sex difference exists for MCAvmean during recovery. Both sexes have lower MCAvmean in hot compared to cool conditions. However, the peripheral vascular mechanisms for this attenuation may differ as females have lower arterial stiffness and higher SVR.

31st g. Heiner sell lectureship: secondary medical consequences of spinal cord injury.

Persons with spinal cord injury (SCI) have secondary medical consequences of paralysis and/or the consequences of extreme inactivity. The metabolic changes that result from reduced activity include insulin resistance with carbohydrate disorders and dyslipidemia. A higher prevalence of coronary artery calcification was found in persons with SCI than that in matched able-bodied controls. A depression in anabolic hormones, circulating testosterone and growth hormone, has been described. Adverse soft tissue body composition changes of increased adiposity and reduced skeletal muscle are appreciated. Immobilization is the cause for sublesional disuse osteoporosis with an associated increased risk of fragility fracture. Bowel dysmotility affects all segments of the gastrointestinal tract, with an interest in better defining and addressing gastroesophageal reflux disease and difficulty with evacuation. Developing and testing more effective approaches to cleanse the bowel for elective colonoscopy are being evaluated. The extent of respiratory dysfunction depends on the level and completeness of SCI. Individuals with higher spinal lesions have both restrictive and obstructive airway disease. Pharmacological approaches and expiratory muscle training are being studied as interventions to improve pulmonary function and cough strength with the objective of reducing pulmonary complications. Persons with spinal lesions above the 6th thoracic level lack both cardiac and peripheral vascular mechanisms to maintain blood pressure, and they are frequently hypotensive, with even worse hypotension with upright posture. Persistent and/or orthostatic hypotension may predispose those with SCI to cognitive impairments. The safety and efficacy of anti-hypotensive agents to normalize blood pressure in persons with higher level cord lesions is being investigated.

Nitric oxide and passive limb movement: a new approach to assess vascular function

Passive limb movement elicits a robust increase in limb blood flow (LBF) and limb vascular conductance (LVC), but the peripheral vascular mechanisms associated with this increase in LBF and LVC are unknown. This study sought to determine the contribution of nitric oxide (NO) to movement-induced LBF and LVC and document the potential for passive-limb movement to assess NO-mediated vasodilatation and therefore NO bioavailability. Six subjects underwent passive knee extension with and without nitric oxide synthase (NOS) inhibition via intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central haemodynamics were measured by finger photoplethysmography. Although L-NMMA did not alter the immediate increase (initial ∼9 s) in LBF and LVC, NOS blockade attenuated the peak increase in LBF (control: 653 ± 81; L-NMMA: 399 ± 112 ml(−1) min(−1), P = 0.03) and LVC (control: 7.5 ± 0.8; L-NMMA: 4.1 ± 1.1 ml min(−1) mmHg(−1), P = 0.02) and dramatically reduced the overall vasodilatory and hyperaemic response (area under the curve) by nearly 80% (LBF: control: 270 ± 51; L-NMMA: 75 ± 32 ml, P = 0.001; LVC: control: 2.9 ± 0.5; L-NMMA: 0.8 ± 0.3 ml mmHg(−1), P < 0.001). Passive movement in control and L-NMMA trials evoked similar increases in heart rate, stroke volume, cardiac output and a reduction in mean arterial pressure. As movement-induced increases in LBF and LVC are predominantly NO dependent, passive limb movement appears to have significant promise as a new approach to assess NO-mediated vascular function, an important predictor of cardiovascular disease risk.

Autonomic nervous system and blood pressure regulation in RGS2-deficient mice

Regulator of G protein signaling (RGS2) deletion in mice prolongs signaling by G protein-coupled vasoconstrictor receptors and increases blood pressure. However, the exact mechanism of the increase in blood pressure is unknown. To address this question we tested autonomic nervous system function and blood pressure regulation in RGS2-deficient mice (RGS2-/-). We measured arterial blood pressure and heart rate (HR) with telemetry, computed time and frequency-domain measures for blood pressure and HR variability (HRV) as well as baroreflex sensitivity [BRS-low frequency (LF)], and assessed environmental stress sensitivity. Mean arterial blood pressure (MAP) was approximately 10 mmHg higher in RGS2-/-compared with RGS2+/+mice, while HR was not different between the groups, indicating a resetting of the baroreceptor reflex. Atropine increased MAP more in RGS2-/-than in RGS2+/+mice while HR responses were not different. Urinary norepinephrine excretion was higher in RGS2-/-than in RGS2+/+mice. The blood pressure decrease following prazosin was more pronounced in RGS2-/-mice than in RGS2+/+mice. The LF and high-frequency (HF) power of HRV were reduced in RGS2-/-compared with controls while BRS-LF and SBP-LF were not different. Atropine and atropine+metoprolol markedly reduced the HRV parameters in the time (RMSSD) and frequency domain (LF, HF, LF/HF) in both strains. Environmental stress sensitivity was increased in RGS2-/-mice compared with controls. We conclude that the increase in blood pressure in RGS2-/-mice is not solely explained by peripheral vascular mechanisms. A central nervous system mechanism might be implicated by an increased sympathetic tone. This state of affairs could lead to a baroreceptor-HR reflex resetting, while BRS remains unimpaired.

Investigations of the peripheral vascular mechanisms implicated in congestive heart failure by the non-invasive evaluation of radial artery compliance and reactivity

The viscoelastic, muscular and endothelial components of the vessel wall may be altered in patients with congestive heart failure (CHF). In order to investigate the relative contribution of each of these components to the peripheral vascular mechanisms of the disease, we have studied post-ischemic (endothelial-dependent) and post-nitroglycerin (endothelial-independent) vasodilatation as well as the response to cold pressure test and the geometry and compliance of the radial artery using a non-invasive echotracking method coupled to digital photoplethysmography. Thirty-nine patients with congestive heart failure (ejection fraction = 28 ± 2%) were compared to age-and sex-matched healthy controls. Baseline therapy was unchanged during the study. In congestive heart failure patients, cross-sectional compliance and volumic distensibility were greater ( P < 0.05) but isobaric compliance which is independent of blood pressure value was unchanged. Post-ischemic and post-nitroglycerin vasodilatation were lower (7 ± 1 vs. 11 ± 1%, P < 0.01 and 6 ± 1 vs. 14 ± 2%, P < 0.001, respectively) and both of the arterial diameter and pressure responses to cold pressor test were blunted (−5 ± 1 vs. −8 ± 1%, P = 0.058 and 6 ± 3 mmHg vs. 13 ± 2 mmHg, P < 0.01, respectively) in congestive heart failure. These changes were similar in primary and ischemic congestive heart failure, suggesting that they are more likely related to common neuro-hormonal factors rather than to an atherosclerotic process.

Investigations of the peripheral vascular mechanisms implicated in congestive heart failure by the non-invasive evaluation of radial artery compliance and reactivity

Investigations of the peripheral vascular mechanisms implicated in congestive heart failure by the non-invasive evaluation of radial artery compliance and reactivity

Reversibility of structural changes in the resistance vessels in hypertension: a review of studies with pindolol.

1. In recent years evidence has accumulated which indicates that although various beta-adrenoceptor antagonists are equally effective in lowering blood pressure in patients with essential hypertension the mechanisms of action of the different drugs are heterogeneous. 2. Pindolol, a beta-adrenoceptor antagonist with pronounced intrinsic sympathomimetic activity (ISA) appears, to some extent, to act via peripheral vascular mechanisms. 3. Following prolonged treatment with pindolol in essential hypertension peripheral vascular resistance at maximal vasodilatation has been found to be decreased compared with the pretreatment values suggesting that the structural vascular changes characteristic of established hypertension may be reversible.

The use of sympathomimetic amines in the treatment of shock

1. The salient features of the various conditions grouped under the heading of “shock” have been briefly considered. Broadly speaking, the principal feature which these conditions share in common is a persistent hypotension the proximate cause of which may be either cardiac or peripheral. 2. The action of the sympathomimetic amines on the cardiac and peripheral vascular mechanisms has been discussed, with particular reference to epinephrine and nor-epinephrine. 3. On the basis of the present experimental evidence we cannot as yet be sure that the use of sympathomimetic amines in the treatment of shock may not be actually harmful rather than beneficial to some patients. It is suggested, therefore, that its use be reserved for clinical investigation, or for patients who are in profound shock, who fail to respond to extensive fluid replacement or other therapeutic procedures, and whose prognosis therefore is very grave under any circumstances.