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Biomedical subjects

Michael E Tschakovsky

Publications and source records attributed to Michael E Tschakovsky.

18 recordsLinked to original sources
PubMed2007

Initial orthostatic hypotension: review of a forgotten condition.

Several studies have shown that standing up is a frequent (3-10%) trigger of loss of consciousness both in young and old subjects. An exaggerated transient BP (blood pressure) fall upon standing is the underlying cause. IOH (initial orthostatic hypotension) is defined as a transient BP decrease within 15 s after standing, >40 mmHg SBP (systolic BP) and/or >20 mmHg DBP (diastolic BP) with symptoms of cerebral hypoperfusion. It differs distinctly from typical orthostatic hypotension (i.e. BP decrease >20 mmHg SBP and/or >10 mmHg DBP after 3 min of standing) as the BP decrease is transient. Only continuous beat-to-beat BP measurement during an active standing-up manoeuvre can document this condition. As IOH is only associated with active rising, passive tilting is of no diagnostic value. The pathophysiology of IOH is thought to be a temporal mismatch between cardiac output and vascular resistance. The marked decrease of vascular resistance during rising is similar to that observed at the onset of leg exercise and is absent during head-up tilting. It is attributed to vasodilatation in the working muscle through local mechanisms. Standing up causes an initial increase in venous return through the effects of contraction of leg and abdominal muscles. The consequent sudden increase in right atrial pressure may contribute to the fall in systemic vascular resistance through a reflex effect. This review alerts clinicians and clinician scientists to a common, yet often neglected, condition that occurs only upon an active change of posture and discusses its epidemiology, pathophysiology and management.

Cardiac Output↗
PubMed2006

Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation?

We investigated the independent contributions of the peak and continued reactive hyperemia on flow-mediated dilation (FMD). 1) For the duration manipulation experiment (DME), 10 healthy males experienced reactive hyperemia durations of 10 s, 20 s, 30 s, 40 s, 50 s, or full reactive hyperemia (RH). 2) For the peak manipulation experiment (PME), eight healthy males experienced reactive hyperemia trials with three peak shear rate magnitudes (large, medium, and small). Data are means +/- SD. For the DME, peak shear rate was not different between trials (P = 0.326). Shear rate area under the curve (AUC) was P < 0.001. Peak %FMD was dependent on shear rate AUC: 10 s, 2.7 +/- 1.3; 20 s, 6.2 +/- 1.9; 30 s, 7.9 +/- 2.9; 40 s, 8.3 +/- 3.2; 50 s, 7.9 +/- 3.2; full RH, 9.3 +/- 4.1, with 10 and 20 s less than full RH (P < 0.001). For the PME, peak shear rate was different between trials (large, 1,049.1 +/- 285.8; medium, 726.4 +/- 228.8; small, 512.8 +/- 161.8; P < 0.001). AUC of the continued shear rate was not (P = 0.412). Peak %FMD was unaffected by peak shear rate (large, 7.0 +/- 2.7%; medium, 7.4 +/- 2.6%; small, 6.6 +/- 1.8%; P = 0.542). Peak and AUC shear stimulus were not significantly related in full RH (r(2) = 0.35, P = 0.07). We conclude that the shear stimulus AUC, not the peak itself, is the critical determinant of the peak FMD response. This indicates AUC as the best method of quantifying reactive hyperemia shear stimulus for %FMD normalization.

Adult↗
PubMed2006

Rapid vasoregulatory mechanisms in exercising human skeletal muscle: dynamic response to repeated changes in contraction intensity.

We tested the hypothesis that vasoregulatory mechanisms exist in humans that can rapidly adjust muscle blood flow to repeated increases and decreases in exercise intensity. Six men and seven women (age, 24.4+/-1.3 yr) performed continuous dynamic forearm handgrip contractions (1- to 2-s contraction-to-relaxation duty cycle) during repeated step increases and decreases in contraction intensity. Three step change oscillation protocols were examined: Slow (7 contractions per contraction intensityx10 steps); Fast (2 contractions per contraction intensityx15 steps); and Very Fast (1 contraction per contraction intensityx15 steps). Forearm blood flow (FBF; Doppler and echo ultrasonography), heart rate (ECG), and mean arterial pressure (arterial tonometry) were examined for the equivalent of a cardiac cycle during each relaxation phase (FBFrelax). Mean arterial pressure and heart rate did not change during repeated step changes (P=0.352 and P=0.190). For both Slow and Fast conditions, relaxation phase FBFrelax adjusted immediately and repeatedly to both increases and decreases in contraction intensity, and the magnitude and time course of FBFrelax changes were virtually identical. For the Very Fast condition, FBFrelax increased with the first contraction and thereafter slowly increased over the course of repeated contraction intensity oscillations. We conclude that vasoregulatory mechanisms exist in human skeletal muscle that are capable of rapidly and repeatedly adjusting muscle blood flow with ongoing step changes in contraction intensity. Importantly, they demonstrate symmetry in response magnitude and time course with increasing versus decreasing contraction intensity but cannot adjust to very fast exercise intensity oscillations.

Adult↗
PubMed2006

Relationship between changes in brachial artery flow-mediated dilation and basal release of nitric oxide in subjects with Type 2 diabetes.

Assessment of flow-mediated dilation (FMD) after forearm ischemia is widely used as a noninvasive bioassay of stimulated nitric oxide (NO)-mediated conduit artery vasodilator function in vivo. Whether this stimulated endothelial NO function reflects basal endothelial NO function is unknown. To test this hypothesis, retrospective analysis of randomized crossover studies was undertaken in 17 subjects with Type 2 diabetes; 9 subjects undertook an exercise training or control period, whereas the remaining 8 subjects were administered an angiotensin II receptor blocker or placebo. FMD was assessed by using wall tracking of high-resolution brachial artery ultrasound images in response to reactive hyperemia. Resistance vessel basal endothelium-dependent NO function was assessed by using intrabrachial administration of NG-monomethyl-L-arginine (L-NMMA) and plethysmographic assessment of forearm blood flow (FBF). FMD was higher after intervention compared with control/placebo (6.15+/-0.53 vs. 3.81+/-0.72%, P<0.001). There were no significant changes in the FBF responses to L-NMMA. Regression analysis between FMD and L-NMMA responses at entry to the study revealed an insignificant correlation (r=-0.10, P=0.7), and improvements in FMD with the interventions were not associated with changes in the L-NMMA responses (r=-0.04, P=0.9). We conclude that conduit artery-stimulated endothelial NO function (FMD) does not reflect basal resistance vessel endothelial NO function in subjects with Type 2 diabetes.

Brachial Artery↗
PubMed2006

Muscular performance after concentric and eccentric exercise in trained men.

PURPOSE: We studied previously resistance-trained men and compared the effects of concentric and eccentric training on performance and structural muscle parameters. METHODS: Seventeen trained individuals (age 26.9 +/- 3.4 yr) participated in 12 wk of either maximum concentric (N = 8) or eccentric (N = 9) resistance training of the elbow flexors. The functional performance was measured as the maximum concentric and eccentric strength and angular velocity at standard loads. Muscle cross-sectional area and cross-sectional area of single cells were used as measures of muscular hypertrophy. Fiber-type proportions were assessed by staining cells for myofibrillar ATPase. RESULTS: Both eccentric and concentric training increased concentric strength to a similar extent (14 vs 18%), whereas eccentric training led to greater increases in eccentric strength than concentric training did (26 vs 9%). The maximum angular velocity at all loads was enhanced equally in both training groups. The cross-sectional area of both the elbow flexors (+11%) and of the type I and type IIA fibers increased only after the eccentric training. In addition, the relative cross-sectional area occupied by the type II fibers increased from 64 to 73% after the eccentric training. There were only minor changes in the fiber-type proportions. CONCLUSION: The present data suggest that for resistance-trained men, increases in concentric strength and velocity performance after eccentric training are largely mediated by changes in fiber and muscle cross-sectional area. However, hypertrophy alone could not explain the increase in eccentric strength. Because the increases in strength and velocity performance after concentric training could not be ascribed to muscular adaptations alone, we suggest that they may be attributable to additional neural factors.

Adult↗
PubMed2006

Muscle blood-flow dynamics at exercise onset: do the limbs differ?

Common approaches to understanding control of muscle blood flow in exercise focus on the contributions of various putative vasoregulatory mechanisms to the magnitude of the steady-state response. The application of systems-control principles offers a unique approach to characterizing and quantifying the non-steady-state adaptation of muscle blood flow with exercise onset. Information gained from this approach provides novel insight into the nature of control mechanisms governing physiological responses to exercise. This review is intended to provide the reader with an understanding of 1) exercise models, methodology for measuring muscle blood flow, and analysis approaches for quantifying muscle blood-flow dynamics; 2) what is currently known about the dynamic response of muscle blood-flow control mechanisms in humans; and 3) the similarities and differences in exercising muscle blood-flow control in the upper versus the lower limbs in humans.

Arm↗
PubMed2005

The relationship between shear stress and flow-mediated dilatation: implications for the assessment of endothelial function.

Endothelium-dependent flow-mediated dilatation (FMD) describes the vasodilatory response of a vessel to elevations in blood flow-associated shear stress. Nitric oxide (NO), one of many vasoactive substances released by the endothelium in response to shear stress, is of particular interest to researchers as it is an antiatherogenic molecule, and a reduction in its bioavailability may play a role in the pathogenesis of vascular disease. The goal of many human studies is to create a shear stress stimulus that produces an NO-dependent response in order to use the FMD measurements as an assay of NO bioavailability. The most common non-invasive technique is the 'reactive hyperaemia test' which produces a large, transient shear stress profile and a corresponding FMD. Importantly, not all FMD is NO mediated and the stimulus creation technique is a critical determinant of NO dependence. The purpose of this review is to (1) explain that the mechanisms of FMD depend on the nature of the shear stress stimulus (stimulus response specificity), (2) provide an update to the current guidelines for FMD assessment, and (3) summarize the issues that surround the clinical utility of measuring both NO- and non-NO-mediated FMD. Future research should include (1) the identification and partitioning of mechanisms responsible for FMD in response to various shear stress profiles, (2) investigation of stimulus response specificity in coronary arteries, and (3) investigation of non-NO FMD mechanisms and their connection to the development of vascular disease and occurrence of cardiovascular events.

Animals↗
PubMed2004

Dynamic response characteristics of local muscle blood flow regulatory mechanisms in human forearm exercise.

We sought to understand the nature of control mechanisms involved in the adaptation of exercising muscle hyperemia. Seven subjects performed rhythmic dynamic forearm exercise under two exercise conditions: small step 1 [step increase from rest to 40% peak forearm vascular conductance (FVC), in ml.min(-1).100 mmHg-1] for 5 min followed by small step 2 (further increase to 80% peak FVC for 5 min), and large step (step increase from rest to 80% peak FVC for 5 min). FVC data were fit with a two- (small step 1) and three-component (small step 2, large step) exponential as appropriate. For the rapid phase I response, FVC dynamic response characteristics (time delay, time constant) were not affected by the magnitude of the work intensity increase when the transition began from rest, but were slower in the 40-80% transition. Rest-80% gain was greater than either rest-40% or 40-80% transitions but represented the same proportion of the phase I + phase II gain across all transitions (57 vs. 56 vs. 57%, respectively, P = 0.975). For the slower phase II response, dynamic response characteristics were not affected by the magnitude of the work intensity increase when initiated from rest. The time constant was not altered when the transition began from exercise vs. rest. We conclude that 1) dynamic response characteristics of exercise hyperemia control mechanisms are not affected by the magnitude of work rate increase when forearm exercise is initiated from rest, 2) phase I but not phase II dynamic response characteristics are sensitive to baseline exercise intensity, and 3) the mechanisms contributing to phase I result in the same relative response magnitude, regardless of the size of the step increase in exercise intensity or the baseline from which it is initiated.

Adaptation, Physiological↗
PubMed2004

Impact of combined NO and PG blockade on rapid vasodilation in a forearm mild-to-moderate exercise transition in humans.

We tested the hypothesis that nitric oxide (NO) and prostaglandins (PGs) contribute to the rapid vasodilation that accompanies a transition from mild to moderate exercise. Nine healthy volunteers (2 women and 7 men) lay supine with forearm at heart level. Subjects were instrumented for continuous brachial artery infusion of saline (control condition) or combined infusion of N(G)-nitro-L-arginine methyl ester (L-NAME) and ketorolac (drug condition) to inhibit NO synthase and cyclooxygenase, respectively. A step increase from 5 min of steady-state mild (5.4 kg) rhythmic, dynamic forearm handgrip exercise (1 s of contraction followed by 2 s of relaxation) to moderate (10.9 kg) exercise for 30 s was performed. Steady-state forearm blood flow (FBF; Doppler ultrasound) and forearm vascular conductance (FVC) were attenuated in drug compared with saline (control) treatment: FBF = 196.8 +/- 30.8 vs. 281.4 +/- 34.3 ml/min and FVC = 179.3 +/- 29.4 vs. 277.8 +/- 34.8 ml.min(-1).100 mmHg(-1) (both P < 0.01). FBF and FVC increased from steady state after release of the initial contraction at the higher workload in saline and drug conditions: DeltaFBF = 72.4 +/- 8.7 and 52.9 +/- 7.8 ml/min, respectively, and DeltaFVC = 66.3 +/- 7.3 and 44.1 +/- 7.0 ml.min(-1).100 mmHg(-1), respectively (all P < 0.05). The percent DeltaFBF and DeltaFVC were not different during saline infusion or combined inhibition of NO and PGs: DeltaFBF = 27.2 +/- 3.1 and 28.1 +/- 3.8%, respectively (P = 0.78) and DeltaFVC = 25.7 +/- 3.2 and 26.0 +/- 4.0%, respectively (P = 0.94). The data suggest that NO and vasodilatory PGs are not obligatory for rapid vasodilation at the onset of a step increase from mild- to moderate-intensity forearm exercise. Additional vasodilatory mechanisms not dependent on NO and PG release contribute to the immediate and early increase in blood flow in an exercise-to-exercise transition.

Adult↗
PubMed2004

Evidence for a rapid vasodilatory contribution to immediate hyperemia in rest-to-mild and mild-to-moderate forearm exercise transitions in humans.

Controversy exists regarding the contribution of a rapid vasodilatory mechanism(s) to immediate exercise hyperemia. Previous in vivo investigations have exclusively examined rest-to-exercise (R-E) transitions where both the muscle pump and early vasodilator mechanisms may be activated. To isolate vasodilatory onset, the present study investigated the onset of exercise hyperemia in an exercise-to-exercise (E-E) transition, where no further increase in muscle pump contribution would occur. Eleven subjects lay supine and performed a step increase from rest to 3 min of mild (10% maximal voluntary contraction), rhythmic, dynamic forearm handgrip exercise, followed by a further step to moderate exercise (20% maximal voluntary contraction) in each of arm above (condition A) or below (condition B) heart level. Beat-by-beat measures of brachial arterial blood flow (Doppler ultrasound) and blood pressure (arterial tonometry) were performed. We observed an immediate increase in forearm vascular conductance in E-E transitions, and the magnitude of this increase matched that of the R-E transitions within each of the arm positions (condition A: E-E, 52.8 +/- 10.7 vs. R-E, 60.3 +/- 11.7 ml.min(-1).100 mmHg(-1), P = 0.66; condition B: E-E, 43.2 +/- 12.8 vs. R-E, 33.9 +/- 8.2 ml.min(-1).100 mmHg(-1), P = 0.52). Furthermore, changes in forearm vascular conductance were identical between R-E and E-E transitions over the first nine contraction-relaxation cycles in condition A. The immediate and identical increase in forearm vascular conductance in R-E and E-E transitions within arm positions provides strong evidence that rapid vasodilation contributes to immediate exercise hyperemia in humans. Specific vasodilatory mechanisms responsible remain to be determined.

Adaptation, Physiological↗
PubMed2004

Impact of controlling shear rate on flow-mediated dilation responses in the brachial artery of humans.

The reactive hyperemia test (RHtest) evokes a transient increase in shear stress as a stimulus for endothelial-dependent flow-mediated vasodilation (EDFMD). We developed a noninvasive method to create controlled elevations in brachial artery (BA) shear rate (SR, estimate of shear stress), controlled hyperemia test (CHtest), and assessed the impact of this vs. the RHtest approach on EDFMD. Eight healthy subjects participated in two trials of each test on 3 separate days. For the CHtest, SR was step increased from 8 to 50 s(-1), created by controlled release of BA compression during forearm heating. For the RHtest, transient increases in SR were achieved after 5 min of forearm occlusion. BA diameter and blood flow velocity (ultrasound) were measured upstream of compression and occlusion sites. Both tests elicited significant dilation (RHtest: 6.33 +/- 3.12%; CHtest: 3.00 +/- 1.05%). The CHtest resulted in 1) reduced between-subject SR and EDFMD variability vs. the RHtest [SR coefficient of variation (CV): 4.9% vs. 36.6%; EDFMD CV: 36.16% vs. 51.80%] and 2) virtual elimination of the impact of BA diameter on the peak EDFMD response (peak EDFMD vs. baseline diameter for RHtest, r(2) = 0.64, P < 0.01, vs. CHtest, r(2) = 0.14, P < 0.01). Normalization of the RHtest EDFMD response to the magnitude of the SR stimulus eliminated test differences in between-subject response variability. Reductions in trial-to-trial and day-to-day SR variability with the CHtest did not reduce EDFMD variability. Between-subject SR variability contributes to EDFMD variability with the RHtest. SR controls with the CHtest or RHtest response normalization are essential for examining EDFMD between groups differing in baseline arterial diameter.

Adult↗
PubMed2004

Immediate exercise hyperemia: contributions of the muscle pump vs. rapid vasodilation.

A striking characteristic of the blood flow adaptation at exercise onset is the immediate and substantial increase in the first few (0-5 s) seconds of exercise. The purpose of this mini-review is to put into context the present evidence regarding mechanisms responsible for this phase of exercise hyperemia. One potential mechanism that has received much attention is the mechanical effect of muscle contraction (the muscle pump). The rapid vasodilatory mechanism(s) is another possible mechanism that has recently been shown to exist. This review will provide the reader with 1) an understanding of the basic physics of blood flow and the theories of muscle pump function, 2) a critical examination of evidence both for and against the contribution of the muscle pump or rapid vasodilatory mechanisms, and 3) an awareness of the limitations and impact of experimental models and exercise modes on the contribution of each of these mechanisms to the immediate exercise hyperemia. The inability to measure microvenular pressure continues to limit investigators to indirect assessments of the muscle pump vs. vasodilatory mechanism contributions to immediate exercise hyperemia in vivo. Future research directions should include examination of muscle-contraction-induced resistance vessel distortion as a trigger for rapid smooth muscle relaxation and further investigation into the exercise mode dependency of muscle pump vs. rapid vasodilatory contributions to immediate exercise hyperemia.

Animals↗
PubMed2003

Nitric oxide and physiologic vasodilation in human limbs: where do we go from here?

This brief review highlights human studies on the role of nitric oxide (NO) and limb vasodilation conducted at the Mayo Clinic over the last 10 years. These studies have attempted to determine whether NO is responsible for the "unexplained" limb vasodilation seen with body heating, limb ischemia, exercise, and mental stress. Our findings are placed in context with data from others, and possible future areas of study are identified.

Body Temperature↗
PubMed2002

Is sympathetic neural vasoconstriction blunted in the vascular bed of exercising human muscle?

Sympathetic vasoconstriction of muscle vascular beds is important in the regulation of systemic blood pressure. However, vasoconstriction during exercise can also compromise blood flow support of muscle metabolism. This study tested the hypothesis that local factors in exercising muscle blunt vessel responsiveness to sympathetic vasoconstriction. We performed selective infusions of three doses of tyramine into the brachial artery (n = 8) to evoke endogenous release of noradrenaline (norepinephrine) at rest and during moderate and heavy rhythmic handgrip exercise. In separate experiments, tyramine was administered during two doses of adenosine infusion (n = 7) and two doses of sodium nitroprusside (SNP) infusion (n = 8). Vasoconstrictor effectiveness across conditions was assessed as the percentage reduction in forearm vascular conductance (FVC), calculated from invasive blood pressure and non-invasive Doppler ultrasound blood flow measurements at the brachial artery. Tyramine evoked a similar dose-dependent vasoconstriction at rest in all three groups, with the highest dose resulting in a 42-46 % reduction in FVC. This vasoconstriction was blunted with increasing exercise intensity (e.g. tyramine high dose percentage reduction in FVC; rest -43.4 +/- 3.7 %, moderate exercise -27.5 +/- 2.3 %, heavy exercise -16.7 +/- 3.6 %; P < 0.05). In contrast, tyramine infusion resulted in a greater percentage reduction in FVC during both doses of adenosine vs. rest (P < 0.05). Finally, percentage change in FVC was greater during low dose SNP infusion vs. rest (P < 0.05), but not different from rest at the high dose of SNP infusion (P = 0.507). A blunted percentage reduction in FVC during endogenous noradrenaline release in exercise but not vasodilator infusion indicates that sympathetic vasoconstriction is blunted in exercising muscle. This blunting appears to be exercise intensity-dependent.

Adenosine↗
PubMed2002

Attenuated vascular responsiveness to noradrenaline release during dynamic exercise in dogs.

During dynamic exercise, there is reduced responsiveness to alpha(1)- and alpha(2)-adrenergic receptor agonists in skeletal muscle vasculature. However, it is desirable to examine the sympathetic responsiveness to endogenous release of neurotransmitter, since exogenous sympathomimetic agents are dependent upon their ability to reach the abluminal receptor. Therefore, to further our understanding of sympathetic control of vasomotor tone during exercise, we employed a technique that would elicit the release of endogenous noradrenaline (norepinephrine) during dynamic exercise. Mongrel dogs (n = 8, 19-24 kg) were instrumented chronically with transit time ultrasound flow probes on both external iliac arteries. A catheter was placed in a side branch of the femoral artery for intra-arterial administration of tyramine, an agent which displaces noradrenaline from the nerve terminal. Doses of 0.5, 1.0 and 3.0 microg ml(-1) min(-1) of iliac blood flow were infused for 1 min at rest and during graded intensities of exercise. Dose-related decreases in iliac vascular conductance were achieved with these concentrations of tyramine. The reductions in iliac vascular conductance (means +/- S.E.M.) were 45 +/- 6 %, 30 +/- 4 %, 26 +/- 3 % and 17 +/- 2 %, for the 1.0 microg ml(-1) min(-1) dose at rest, 3.0 miles h(-1), 6.0 miles h(-1) and 6.0 miles h(-1), 10 % gradient, respectively. At all doses, the magnitude of vasoconstriction caused by administration of tyramine was inversely related to workload. We conclude that there is a reduced vascular responsiveness to sympathoactivation in dynamically exercising skeletal muscle.

Adrenergic alpha-Agonists↗