Influence of heart rate on fractional flow reserve, pressure drop coefficient, and lesion flow coefficient for epicardial coronary stenosis in a porcine model

A limitation in the use of invasive coronary diagnostic indexes is that fluctuations in hemodynamic factors such as heart rate (HR), blood pressure, and contractility may alter resting or hyperemic flow measurements and may introduce uncertainties in the interpretation of these indexes. In this study, we focused on the effect of fluctuations in HR and area stenosis (AS) on diagnostic indexes. We hypothesized that the pressure drop coefficient (CDP(e), ratio of transstenotic pressure drop and distal dynamic pressure), lesion flow coefficient (LFC, square root of ratio of limiting value CDP and CDP at site of stenosis) derived from fluid dynamics principles, and fractional flow reserve (FFR, ratio of average distal and proximal pressures) are independent of HR and can significantly differentiate between the severity of stenosis. Cardiac catheterization was performed on 11 Yorkshire pigs. Simultaneous measurements of distal coronary arterial pressure and flow were performed using a dual sensor-tipped guidewire for HR < 120 and HR > 120 beats/min, in the presence of epicardial coronary lesions of <50% AS and >50% AS. The mean values of FFR, CDP(e), and LFC were significantly different (P < 0.05) for lesions of <50% AS and >50% AS (0.88 ± 0.04, 0.76 ± 0.04; 62 ± 30, 151 ± 35, and 0.10 ± 0.02 and 0.16 ± 0.01, respectively). The mean values of FFR and CDP(e) were not significantly different (P > 0.05) for variable HR conditions of HR < 120 and HR > 120 beats/min (FFR, 0.81 ± 0.04 and 0.82 ± 0.04; and CDP(e), 95 ± 33 and 118 ± 36). The mean values of LFC do somewhat vary with HR (0.14 ± 0.01 and 0.12 ± 0.02). In conclusion, fluctuations in HR have no significant influence on the measured values of CDP(e) and FFR but have a marginal influence on the measured values of LFC. However, all three parameters can significantly differentiate between stenosis severities. These results suggest that the diagnostic parameters can be potentially used in a better assessment of coronary stenosis severity under a clinical setting.     

Influence of coronary collateral flow on coronary diagnostic parameters: An in vitro study

Functional severity of coronary stenosis is often assessed using diagnostic parameters. These parameters are evaluated from the combined pressure and/or flow measurements taken at the site of the stenosis. However, when there are functional collaterals operating downstream to the stenosis, the coronary flow-rate increases, and the pressure in the stenosed artery is altered. This effect of downstream collaterals on different diagnostic parameters is studied using a physiological representative in vitro coronary flow-loop.The three diagnostic parameters tested are fractional flow reserve (FFR), lesion flow coefficient (LFC), and pressure drop coefficient (CDP). The latter two were discussed in recent publications by our group (Banerjee et al., 2008, Banerjee et al., 2007, 2009). They are evaluated for three different severities of stenosis and tested for possible misinterpretation in the presence of variable collateral flows. Pressure and flow are measured with and without downstream collaterals. The diagnostic parameters are then calculated from these readings.In the case of intermediate stenosis (80% area blockage), FFR and LFC increased from 0.74 to 0.77 and 0.58 to 0.62, respectively, for no collateral to fully developed collateral flow. Also, CDP decreased from 47 to 42 for no collateral to fully developed collateral flow. These changes in diagnostic parameters might lead to erroneous postponement of coronary intervention. Thus, variability in diagnostic parameters for the same stenosis might lead to misinterpretation of stenosis severity in the presence of operating downstream collaterals.     

Influence of arterial wall-stenosis compliance on the coronary diagnostic parameters

Functional diagnostic parameters such as Fractional Flow Reserve (FFR), which is calculated from pressure measurements across stenosed arteries, are often used to determine the functional severity of coronary artery stenosis. This study evaluated the effect of arterial wall-stenosis compliance, with limiting scenarios of stenosis severity, on the diagnostic parameters. The diagnostic parameters considered in this study include an established index, FFR and two recently developed parameters: Pressure Drop Coefficient (CDP) and Lesion Flow Coefficient (LFC). The parameters were assessed for rigid artery (RR; signifying high plaque elasticity), compliant artery with calcified plaque (CC; intermediate plaque elasticity) and compliant artery with smooth muscle cell proliferation (CS; low plaque elasticity), with varying degrees of epicardial stenosis. A hyperelastic Mooney-Rivlin model was used to model the arterial wall and plaque materials. Blood was modeled as a shear thinning, non-Newtonian fluid using the Carreau model. The arterial wall compliance was evaluated using the finite element method. The present study found that, with an increase in stenosis severity, FFR decreased whereas CDP and LFC increased. The cutoff value of 0.75 for FFR was observed at 78.7% area stenosis for RR, whereas for CC and CS the cutoff values were obtained at higher stenosis severities of 81.3% and 82.7%, respectively. For a fixed stenosis, CDP value decreased and LFC value increased with a decrease in plaque elasticity (RR to CS). We conclude that the differences in diagnostic parameters with compliance at intermediate stenosis (78.7-82.7% area blockage) could lead to misinterpretation of the stenosis severity.     

Acute effects of stretching exercise on the heart rate variability in subjects with low flexibility levels

The study investigated the heart rate (HR) and heart rate variability (HRV) before, during, and after stretching exercises performed by subjects with low flexibility levels. Ten men (age: 23 ± 2 years; weight: 82 ± 13 kg; height: 177 ± 5 cm; sit-and-reach: 23 ± 4 cm) had the HR and HRV assessed during 30 minutes at rest, during 3 stretching exercises for the trunk and hamstrings (3 sets of 30 seconds at maximum range of motion), and after 30 minutes postexercise. The HRV was analyzed in the time ('SD of normal NN intervals' [SDNN], 'root mean of the squared sum of successive differences' [RMSSD], 'number of pairs of adjacent RR intervals differing by >50 milliseconds divided by the total of all RR intervals' [PNN50]) and frequency domains ('low-frequency component' [LF], 'high-frequency component' [HF], LF/HF ratio). The HR and SDNN increased during exercise (p < 0.03) and decreased in the postexercise period (p = 0.02). The RMSSD decreased during stretching (p = 0.03) and increased along recovery (p = 0.03). At the end of recovery, HR was lower (p = 0.01), SDNN was higher (p = 0.02), and PNN50 was similar (p = 0.42) to pre-exercise values. The LF increased (p = 0.02) and HF decreased (p = 0.01) while stretching, but after recovery, their values were similar to pre-exercise (p = 0.09 and p = 0.3, respectively). The LF/HF ratio increased during exercise (p = 0.02) and declined during recovery (p = 0.02), albeit remaining higher than at rest (p = 0.03). In conclusion, the parasympathetic activity rapidly increased after stretching, whereas the sympathetic activity increased during exercise and had a slower postexercise reduction. Stretching sessions including multiple exercises and sets acutely changed the sympathovagal balance in subjects with low flexibility, especially enhancing the postexercise vagal modulation.     

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.     

Carotid baroreflex responsiveness is impaired in normotensive African American men

There are important differences in autonomic function and cardiovascular responsiveness between African Americans (AA) and Caucasian Americans (CA). This study tested the hypothesis that carotid baroreflex (CBR) responsiveness is impaired in normotensive AA compared with normotensive CA at rest. CBR control of heart rate (HR) and mean arterial blood pressure (MAP) was assessed in 30 nonhypertensive male subjects (15 AA; 15 CA; age 18-33 yr) with 5-s periods of neck pressure (NP; simulated hypotension) and neck suction (NS; simulated hypertension) ranging from +45 to -80 Torr during rest. Carotid-cardiac stimulus-response curves revealed a significantly lower minimum HR response in the CA compared with AA (40.8 ± 2.4 vs. 49.8 ± 2.9 beats/min, respectively; P < 0.05). In addition, the magnitude of the mean HR response to all trials of NS (-20, -40, -60, and -80 Torr) was attenuated in the AA group (AA, -10.1 ± 1.7 vs. CA, -14.9 ± 2.2 beats/min; P < 0.05), while no significant differences were found in the magnitude of the mean HR response to NP (+15, +30, and +45 Torr) between racial groups. There were no significant differences in the carotid-vasomotor stimulus-response curves between racial groups. Also, while no racial differences were found in the magnitude of the mean MAP response to all trials of NS, the magnitude of the mean MAP response to all trials of NP was attenuated in the AA group (AA, 7.2 ± 1.3 vs. CA, 9.3 ± 1.1 mmHg; P < 0.05). Together, these findings support inherent differences in short-term blood pressure regulation between racial groups that exhibit different relative risk for the development of hypertension.     

Heart rate modulates the slow enhancement of contraction due to sudden left ventricular dilation

In isovolumic blood-perfused dog hearts, left ventricular developed pressure (DP) was recorded while a sudden ventricular dilation was promoted at three heart rate (HR) levels: low (L: 52 +/- 1.7 beats/min), intermediate (M: 82 +/- 2.2 beats/min), and high (H: 117 +/- 3.5 beats/min). DP increased instantaneously with chamber expansion (Delta(1)DP), and another continuous increase occurred for several minutes (Delta(2)DP). HR elevation did not alter Delta(1)DP (32.8 +/- 1.6, 33.6 +/- 1.5, and 34.3 +/- 1.2 mmHg for L, M, and H, respectively), even though it intensified Delta(2)DP (17.3 +/- 0.9, 20.7 +/- 1.0, and 26.8 +/- 1.2 mmHg for L, M, and H, respectively), meaning that the treppe phenomenon enhances the length dependence of the contraction component related to changes in intracellular Ca(2+) concentration. Frequency increments reduced the half time of the slow response (82 +/- 3.6, 67 +/- 2.6, and 53 +/- 2.0 s for L, M, and H, respectively), while the number of beats included in half time increased (72 +/- 2.9, 95 +/- 2.9, and 111 +/- 3.2 beats for L, M, and H, respectively). HR modulation of the slow response suggests that L-type Ca(2+) channel currents and/or the Na(+)/Ca(2+) exchanger plays a relevant role in the stretch-triggered Ca(2+) gain when HR increases in the canine heart.     

Genetic evaluation of Ethiopian Boran cattle and their crosses with Holstein Friesian in central Ethiopia: milk production traits

Breed additive and non-additive effects, and genetic parameters of lactation milk yield (LYD), 305-day milk yield (305YD), lactation length (LL), milk yield per day of lactation (DM) and lifetime milk yield (LTYD) were estimated in Ethiopian Boran cattle and their crosses with Holstein in central Ethiopia. The data analyzed included 2360 lactation records spread over 15 years. Ethiopian Boran cattle were consistently inferior (P < 0.01) to the Ethiopian Boran-Holstein crosses for the dairy traits studied. When the crosses were compared, LYD, 305YD and DM were higher (P < 0.01) for 75% and 87.5% crosses compared to 50% and 62.5% ones. However, the 50% crosses had higher (P < 0.01) LTYD than the other genetic groups. The individual additive genetic breed differences for milk production traits were all significant (P < 0.01). The estimates, in favor of Holstein, were 2055 ± 192 kg for LYD, 1776 ± 142 kg for 305YD, 108 ± 24 days for LL, 5.9 ± 0.5 kg for DM and 3353 ± 1294 kg for LTYD. Crossbreeding of the Holstein with the Ethiopian Boran resulted in desirable and significant (P < 0.01) individual heterosis for all milk production traits. The heterosis estimates were, 529 ± 98, 427 ± 72 kg, 44 ± 12 days 1.47 ± 0.23 kg and 3337 ± 681 kg, for LYD, 305YD, LL, DM and LTYD, respectively. The maternal heterotic effects were non-significant (P > 0.05) for all traits. Heritabilities of LYD, 305YD, LL, DM and LTYD for Ethiopian Boran were 0.20 ± 0.03, 0.18 ± 0.03, 0.26 ± 0.03, 0.13 ± 0.03 and 0.02 ± 0.04, respectively. The corresponding estimates for crosses were 0.10 ± 0.002, 0.11 ± 0.003, 0.63 ± 0.02, 0.45 ± 1.05 and 0.24 ± 0.11, respectively. Selection within each of the genetic groups and crossbreeding should substantially improve the milk production potential of the Ethiopian Boran breed under such production system.     

Influence of newly designed monorail pressure sensor catheter on coronary diagnostic parameters: An in vitro study

The decision to perform intervention on a patient with coronary stenosis is often based on functional diagnostic parameters obtained from pressure and flow measurements using sensor-tipped guidewire at maximal vasodilation (hyperemia). Recently, a rapid exchange Monorail Pressure Sensor catheter of 0.022″ diameter (MPS22), with pressure sensor at distal end has been developed for improved assessment of stenosis severity. The hollow shaft of the MPS22 is designed to slide over any standard 0.014″ guidewire (G14). Hence, influence of MPS22 diameter on coronary diagnostic parameters needs investigation. An in vitro experiment was conducted to replicate physiologic flows in three representative area stenosis (AS): mild (64% AS), intermediate (80% AS), and severe (90% AS), for two arterial diameters, 3 mm (N2; more common) and 2.5 mm (N1). Influence of MPS22 on diagnostic parameters: fractional flow reserve (FFR) and pressure drop coefficient (CDP) was evaluated both at hyperemic and basal conditions, while comparing it with G14. The FFR values decreased for the MPS22 in comparison to G14, (Mild: 0.87 vs 0.88, Intermediate: 0.68 vs 0.73, Severe: 0.48 vs 0.56) and CDP values increased (Mild: 16 vs 14, Intermediate: 75 vs 56, Severe: 370 vs 182) for N2. Similar trend was observed in the case of N1. The FFR values were found to be well above (mild) and below (intermediate and severe) the diagnostic cut-off of 0.75. Therefore, MPS22 catheter can be used as a possible alternative to G14. Further, irrespective of the MPS22 or G14, basal FFR (FFR_b) had overlapping ranges in close proximity for clinically relevant mild and intermediate stenoses that will lead to diagnostic uncertainty under both N1 and N2. However, CDP_b had distinct ranges for different stenosis severities and could be a potential diagnostic parameter under basal conditions.     

Relationships between the extent of apnea-induced bradycardia and the vascular response in the arm and leg during dynamic two-legged knee extension exercise

Our aim was to test the hypothesis that apnea-induced hemodynamic responses during dynamic exercise in humans differ between those who show strong bradycardia and those who show only mild bradycardia. After apnea-induced changes in heart rate (HR) were evaluated during dynamic exercise, 23 healthy subjects were selected and divided into a large response group (L group; n = 11) and a small response group (S group; n = 12). While subjects performed a two-legged dynamic knee extension exercise at a work load that increased HR by 30 beats/min, apnea-induced changes in HR, cardiac output (CO), mean arterial pressure (MAP), arterial O(2) saturation (Sa(O(2))), forearm blood flow (FBF), and leg blood flow (LBF) were measured. During apnea, HR in the L group (54 ± 2 beats/min) was lower than in the S group (92 ± 3 beats/min, P < 0.05). CO, Sa(O(2)), FBF, LBF, forearm vascular conductance (FVC), leg vascular conductance (LVC), and total vascular conductance (TVC) were all reduced, and MAP was increased in both groups, although the changes in CO, TVC, LBF, LVC, and MAP were larger in the L group than in the S group (P < 0.05). Moreover, there were significant positive linear relationships between the reduction in HR and the reductions in TVC, LVC, and FVC. We conclude that individuals who show greater apnea-induced bradycardia during exercise also show greater vasoconstriction in both active and inactive muscle regions.     

Excessive heart rate response to orthostatic stress in postural tachycardia syndrome is not caused by anxiety.

Postural tachycardia syndrome (POTS) is characterized by excessive increases in heart rate (HR) without hypotension during orthostasis. The relationship between the tachycardia and anxiety is uncertain. Therefore, we tested whether the HR response to orthostatic stress in POTS is primarily related to psychological factors. POTS patients (n = 14) and healthy controls (n = 10) underwent graded venous pooling with lower body negative pressure (LBNP) to -40 mmHg while wearing deflated antishock trousers. "Sham" venous pooling was performed by 1) trouser inflation to 5 mmHg during LBNP and 2) vacuum pump activation without LBNP. HR responses to mental stress were also measured in both groups, and a questionnaire was used to measure psychological parameters. During LBNP, HR in POTS patients increased 39 +/- 5 beats/min vs. 19 +/- 3 beats/min in control subjects at -40 mmHg (P < 0.01). LBNP with trouser inflation markedly blunted the HR responses in the patients (9 +/- 2 beats/min) and controls (2 +/- 1 beats/min), and there was no HR increase during vacuum application without LBNP in either group. HR responses during mental stress were not different in the patients and controls (18 +/- 2 vs. 19 +/- 1 beats/min; P > 0.6). Anxiety, somatic vigilance, and catastrophic cognitions were significantly higher in the patients (P < 0.05), but they were not related to the HR responses during LBNP or mental stress (P > 0.1). These results suggest that the HR response to orthostatic stress in POTS patients is not caused by anxiety but that it is a physiological response that maintains arterial pressure during venous pooling.     

Moderate weight loss improves heart rate variability in overweight and obese adults with type 2 diabetes

The objective of this study was to determine the effects of weight loss on heart rate variability (HRV) and its association with traditional cardiovascular disease risk factors in overweight and obese patients with type 2 diabetes. Forty five patients [body mass index (BMI) 35.4 ± 0.7 kg/m2; age 56.5 ± 1.1 yr] with type 2 diabetes followed an energy-restricted diet (6-7 MJ/day) for 16 wk. Body weight, blood pressure, glucose, insulin, insulin resistance [homeostasis model assessment index 2 (HOMA2)], glycosylated hemoglobin (HbA1c), total cholesterol, low-density lipoproteins (LDL), high-density lipoproteins (HDL), triglycerides, resting HR, and HRV were measured before and after the intervention period. Mean reduction in body weight was 11.1 ± 1.0 kg (10%), with significant reductions in blood pressure (-10%), total cholesterol (-15.9%), LDL (-17.7%), HDL (-7.5%), triglycerides (-21.2%), glucose (-23.4%), insulin (-37.6%), HOMA2 (-40.1%), and HbA1c (-14.5%) (P ≤ 0.05 for all variables). There were increases in several HRV components, including total power (1,370 ± 280 to 2,045 ± 280 ms2), low-frequency power (345 ± 70 to 600 ± 108 ms2), SD of normal to normal intervals (SDNN; 35.0 ± 2.5 to 43.0 ± 2.7 s), and square root of the mean squared differences of successive normal to normal intervals (RMSSD; 23.0 ± 3.5 to 32.0 ± 3.1 s), and a decrease in HR (69.0 ± 1.3 to 60.0 ± 1.2 beats/min) (P ≤ 0.03 for all variables). Changes in HR, SDNN, total power, and low-frequency power correlated with change in BMI (P < 0.05). In addition to improvements in traditional cardiovascular and metabolic risk factors, weight loss improves HRV in overweight and obese patients with type 2 diabetes.     

Effects of avertin versus xylazine-ketamine anesthesia on cardiac function in normal mice

Anesthetic regimens commonly administered during studies that assess cardiac structure and function in mice are xylazine-ketamine (XK) and avertin (AV). While it is known that XK anesthesia produces more bradycardia in the mouse, the effects of XK and AV on cardiac function have not been compared. We anesthetized normal adult male Swiss Webster mice with XK or AV. Transthoracic echocardiography and closed-chest cardiac catheterization were performed to assess heart rate (HR), left ventricular (LV) dimensions at end diastole and end systole (LVDd and LVDs, respectively), fractional shortening (FS), LV end-diastolic pressure (LVEDP), the time constant of isovolumic relaxation (tau), and the first derivatives of LV pressure rise and fall (dP/dt(max) and dP/dt(min), respectively). During echocardiography, HR was lower in XK than AV mice (250 +/- 14 beats/min in XK vs. 453 +/- 24 beats/min in AV, P < 0.05). Preload was increased in XK mice (LVDd: 4.1 +/- 0.08 mm in XK vs. 3.8 +/- 0.09 mm in AV, P < 0.05). FS, a load-dependent index of systolic function, was increased in XK mice (45 +/- 1.2% in XK vs. 40 +/- 0.8% in AV, P < 0.05). At LV catheterization, the difference in HR with AV (453 +/- 24 beats/min) and XK (342 +/- 30 beats/min, P < 0.05) anesthesia was more variable, and no significant differences in systolic or diastolic function were seen in the group as a whole. However, in XK mice with HR <300 beats/min, LVEDP was increased (28 +/- 5 vs. 6.2 +/- 2 mmHg in mice with HR >300 beats/min, P < 0.05), whereas systolic (LV dP/dt(max): 4,402 +/- 798 vs. 8,250 +/- 415 mmHg/s in mice with HR >300 beats/min, P < 0.05) and diastolic (tau: 23 +/- 2 vs. 14 +/- 1 ms in mice with HR >300 beats/min, P < 0.05) function were impaired. Compared with AV, XK produces profound bradycardia with effects on loading conditions and ventricular function. The disparate findings at echocardiography and LV catheterization underscore the importance of comprehensive assessment of LV function in the mouse.     

Arterial baroreflex control of heart rate during exercise in postural tachycardia syndrome.

Patients with postural tachycardia syndrome (POTS) have excessive tachycardia without hypotension during orthostasis as well as exercise. We tested the hypothesis that excessive tachycardia during exercise in POTS is not related to abnormal baroreflex control of heart rate (HR). Patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter) and HR (ECG) were measured. Baroreflex sensitivity of HR was assessed by bolus intravenous infusion of phenylephrine at each workload. In both positions, HR was higher in the patients than the controls during exercise. Supine baroreflex sensitivity (HR/systolic pressure) in POTS patients was -1.3 +/- 0.1 beats.min(-1).mmHg(-1) at rest and decreased to -0.6 +/- 0.1 beats.min(-1).mmHg(-1) during 75-W exercise, neither significantly different from the controls (P > 0.6). In the upright position, baroreflex sensitivity in POTS patients at rest (-1.4 +/- 0.1 beats.min(-1).mmHg(-1)) was higher than the controls (-1.0 +/- 0.1 beats.min(-1).mmHg(-1)) (P < 0.05), and it decreased to -0.1 +/- 0.04 beats.min(-1).mmHg(-1) during 75-W exercise, lower than the controls (-0.3 +/- 0.09 beats.min(-1).mmHg(-1)) (P < 0.05). The reduced arterial baroreflex sensitivity of HR during upright exercise was accompanied by greater fluctuations in systolic and pulse pressure in the patients than in the controls with 56 and 90% higher coefficient of variations, respectively (P < 0.01). However, when baroreflex control of HR was corrected for differences in HR, it was similar between the patients and controls during upright exercise. These results suggest that the tachycardia during exercise in POTS was not due to abnormal baroreflex control of HR.     

Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.     

Early Reperfusion Hemodynamics Predict Recovery in Rat Hearts: A Potential Approach towards Evaluating Cardiac Grafts from Non-Heart-Beating Donors

Aims

Cardiac grafts from non-heartbeating donors (NHBDs) could significantly increase organ availability and reduce waiting-list mortality. Reluctance to exploit hearts from NHBDs arises from obligatory delays in procurement leading to periods of warm ischemia and possible subsequent contractile dysfunction. Means for early prediction of graft suitability prior to transplantation are thus required for development of heart transplantation programs with NHBDs.

Methods and Results

Hearts (n = 31) isolated from male Wistar rats were perfused with modified Krebs-Henseleit buffer aerobically for 20 min, followed by global, no-flow ischemia (32°C) for 30, 50, 55 or 60 min. Reperfusion was unloaded for 20 min, and then loaded, in working-mode, for 40 min. Left ventricular (LV) pressure was monitored using a micro-tip pressure catheter introduced via the mitral valve. Several hemodynamic parameters measured during early, unloaded reperfusion correlated significantly with LV work after 60 min reperfusion (p<0.001). Coronary flow and the production of lactate and lactate dehydrogenase (LDH) also correlated significantly with outcomes after 60 min reperfusion (p<0.05). Based on early reperfusion hemodynamic measures, a composite, weighted predictive parameter, incorporating heart rate (HR), developed pressure (DP) and end-diastolic pressure, was generated and evaluated against the HR-DP product after 60 min of reperfusion. Effective discriminating ability for this novel parameter was observed for four HR*DP cut-off values, particularly for ≥20 *10³ mmHg*beats*min⁻¹ (p<0.01).

Conclusion

Upon reperfusion of a NHBD heart, early evaluation, at the time of organ procurement, of cardiac hemodynamic parameters, as well as easily accessible markers of metabolism and necrosis seem to accurately predict subsequent contractile recovery and could thus potentially be of use in guiding the decision of accepting the ischemic heart for transplantation.     

Low-dose estrogen therapy does not change postexercise hypotension, sympathetic nerve activity reduction, and vasodilation in healthy postmenopausal women

The aim of this study was to determine whether estrogen therapy enhances postexercise muscle sympathetic nerve activity (MSNA) decrease and vasodilation, resulting in a greater postexercise hypotension. Eighteen postmenopausal women received oral estrogen therapy (ET; n=9, 1 mg/day) or placebo (n=9) for 6 mo. They then participated in one 45-min exercise session (cycle ergometer at 50% of oxygen uptake peak) and one 45-min control session (seated rest) in random order. Blood pressure (BP, oscillometry), heart rate (HR), MSNA (microneurography), forearm blood flow (FBF, plethysmography), and forearm vascular resistance (FVR) were measured 60 min later. FVR was calculated. Data were analyzed using a two-way ANOVA. Although postexercise physiological responses were unaltered, HR was significantly lower in the ET group than in the placebo group (59+/-2 vs. 71+/-2 beats/min, P<0.01). In both groups, exercise produced significant decreases in systolic BP (145+/-3 vs. 154+/-3 mmHg, P=0.01), diastolic BP (71+/-3 vs. 75+/-2 mmHg, P=0.04), mean BP (89+/-2 vs. 93+/-2 mmHg, P=0.02), MSNA (29+/-2 vs. 35+/-1 bursts/min, P<0.01), and FVR (33+/-4 vs. 55+/-10 units, P=0.01), whereas it increased FBF (2.7+/-0.4 vs. 1.6+/-0.2 ml x min(-1) x 100 ml(-1), P=0.02) and did not change HR (64+/-2 vs. 65+/-2 beats/min, P=0.3). Although ET did not change postexercise BP, HR, MSNA, FBF, or FVR responses, it reduced absolute HR values at baseline and after exercise.     

Exercise training augments the dynamic heart rate response to vagal but not sympathetic stimulation in rats

We examined the transfer function of autonomic heart rate (HR) control in anesthetized sedentary and exercise-trained (16 wk, treadmill for 1 h, 5 times/wk at 15 m/min and 15-degree grade) rats for comparison to HR variability assessed in the conscious resting state. The transfer function from sympathetic stimulation to HR response was similar between groups (gain, 4.2 ± 1.5 vs. 4.5 ± 1.5 beats·min(-1)·Hz(-1); natural frequency, 0.07 ± 0.01 vs. 0.08 ± 0.01 Hz; damping coefficient, 1.96 ± 0.55 vs. 1.69 ± 0.15; and lag time, 0.7 ± 0.1 vs. 0.6 ± 0.1 s; sedentary vs. exercise trained, respectively, means ± SD). The transfer gain from vagal stimulation to HR response was 6.1 ± 3.0 in the sedentary and 9.7 ± 5.1 beats·min(-1)·Hz(-1) in the exercise-trained group (P = 0.06). The corner frequency (0.11 ± 0.05 vs. 0.17 ± 0.09 Hz) and lag time (0.1 ± 0.1 vs. 0.2 ± 0.1 s) did not differ between groups. When the sympathetic transfer gain was averaged for very-low-frequency and low-frequency bands, no significant group effect was observed. In contrast, when the vagal transfer gain was averaged for very-low-frequency, low-frequency, and high-frequency bands, exercise training produced a significant group effect (P < 0.05 by two-way, repeated-measures ANOVA). These findings suggest that, in the frequency domain, exercise training augments the dynamic HR response to vagal stimulation but not sympathetic stimulation, regardless of the frequency bands.     

Reduced stroke volume during exercise in postural tachycardia syndrome.

Postural tachycardia syndrome (POTS) is characterized by excessive tachycardia without hypotension during orthostasis. Most POTS patients also report exercise intolerance. To assess cardiovascular regulation during exercise in POTS, patients (n = 13) and healthy controls (n = 10) performed graded cycle exercise at 25, 50, and 75 W in both supine and upright positions while arterial pressure (arterial catheter), heart rate (HR; measured by ECG), and cardiac output (open-circuit acetylene breathing) were measured. In both positions, mean arterial pressure, cardiac output, and total peripheral resistance at rest and during exercise were similar in patients and controls (P > 0.05). However, supine stroke volume (SV) tended to be lower in the patients than controls at rest (99 +/- 5 vs. 110 +/- 9 ml) and during 75-W exercise (97 +/- 5 vs. 111 +/- 7 ml) (P = 0.07), and HR was higher in the patients than controls at rest (76 +/- 3 vs. 62 +/- 4 beats/min) and during 75-W exercise (127 +/- 3 vs. 114 +/- 5 beats/min) (both P < 0.01). Upright SV was significantly lower in the patients than controls at rest (57 +/- 3 vs. 81 +/- 6 ml) and during 75-W exercise (70 +/- 4 vs. 94 +/- 6 ml) (both P < 0.01), and HR was much higher in the patients than controls at rest (103 +/- 3 vs. 81 +/- 4 beats/min) and during 75-W exercise (164 +/- 3 vs. 131 +/- 7 beats/min) (both P < 0.001). The change (upright - supine) in SV was inversely correlated with the change in HR for all participants at rest (R(2) = 0.32), at 25 W (R(2) = 0.49), 50 W (R(2) = 0.60), and 75 W (R(2) = 0.32) (P < 0.01). These results suggest that greater elevation in HR in POTS patients during exercise, especially while upright, was secondary to reduced SV and associated with exercise intolerance.     

Genetic locus on mouse chromosome 7 controls elevated heart rate

Elevated heart rate (HR) is a risk factor for cardiovascular diseases. The goal of the study was to map HR trait in mice using quantitative trait locus (QTL) analysis followed by genome-wide association (GWA) analysis. The first approach provides mapping power and the second increases genome resolution. QTL analyses were performed in a C3HeB×SJL backcross. HR and systolic blood pressure (SBP) were measured by the tail-cuff plethysmography. HR was ～80 beats/min higher in SJL compared with C3HeB. There was a wide distribution of the HR (536-763 beats/min) in N2 mice. We discovered a highly significant QTL (logarithm of odds = 6.7, P < 0.001) on chromosome 7 (41 cM) for HR in the C3HeB×SJL backcross. In the Hybrid Mouse Diversity Panel (58 strains, n = 5-6/strain) we found that HR (beats/min) ranged from 546 ± 12 in C58/J to 717 ± 7 in MA/MyJ mice. SBP (mmHg) ranged from 99 ± 6 in strain I/LnJ to 151 ± 4 in strain BXA4/PgnJ. GWA analyses were done using the HMDP, which revealed a locus (64.2-65.1 Mb) on chromosome 7 that colocalized with the QTL for elevated HR found in the C3HeB×SJL backcross. The peak association was observed for 17 SNPs that are localized within three GABA(A) receptor genes. In summary, we used a combined genetic approach to fine map a novel elevated HR locus on mouse chromosome 7.