Effects of hypovolemia on aortic baroreflex control of heart rate in humans

INTRODUCTION: To test the hypothesis that hypovolemia can acutely increase the sensitivity of chronotropic baroreflex response, eight men (21-45 yr old) underwent measurements of heart rate response to aortic baroreceptor stimulation under normovolemic and hypovolemic conditions. METHODS: Hypovolemia was acutely induced by a bolus injection of 30 mg of furosemide. The sensitivity of the aortic-cardiac baroreflex was determined with a approximately 15 mmHg elevation in mean arterial pressure (MAP) induced by steady-state infusion of 30 to 97 micrograms.min-1 phenylephrine (PE) combined with approximately 13 mmHg lower body negative pressure (LBNP) to counteract central venous pressure elevations, and 17-19 mmHg neck pressure (NP) to offset increases in carotid sinus transmural pressure. The aortic-cardiac baroreflex gain was assessed by determining the ratio of the change in heart rate to the change in MAP (delta HR/delta MAP) between baseline and aortic baroreceptor isolated conditions (i.e., PE + LBNP + NP stage). RESULTS: When compared to normovolemia (3182 +/- 163 ml), furosemide-induced hypovolemia (2812 +/- 101 ml) resulted in an average 12% reduction in plasma volume (p = 0.05). Hypovolemia increased the average gain of the aortic-cardiac baroreflex by 68% (0.71 +/- 0.26 to 1.19 +/- 0.37 beats.min-1.mmHg-1; p = 0.0349) while it had no effect on the calculated response of the carotid-cardiac baroreflex. CONCLUSIONS: These results indicate that greater aortic baroreflex sensitivity observed in individuals who are physically untrained or have been exposed to microgravity may be explained by smaller vascular volume rather than differences in autonomic function associated with adaptations to lower aerobic capacity.     

Evaluation of the isolated paced rat heart

Ventricular performance and coronary flow in Langendorff perfused rat hearts were measured over a wide range of perfusion pressures and heart rates. A change in aortic pressure from 60 to 120 mmHg induced a linear increase in coronary flow, ventricular systolic pressure, and contractility. Ventricular pacing from 300 to 600 beats/min under a constant afterload had no effect on coronary flow. Systolic pressure remained stable up to 400-450 beats/min and then decreased 14% at 600 beats/min compared to the nonpaced controls. When contraction rate exceeded 450 beats/min diastolic pressure progressively increased as the heart rate was elevated. Contractility decreased rapidly between 450 and 600 beats/min under all perfusion pressures. These data indicate that this heart model is physiologically stable with heart rates less than 450 beats/min and may be useful in studying tachycardia-induced work overload.     

Mechanisms for increasing stroke volume during static exercise with fixed heart rate in humans

Ten patients with preserved inotropic function having a dual-chamber (right atrium and right ventricle) pacemaker placed for complete heart block were studied. They performed static one-legged knee extension at 20% of their maximal voluntary contraction for 5 min during three conditions: 1) atrioventricular sensing and pacing mode [normal increase in heart rate (HR; DDD)], 2) HR fixed at the resting value (DOO-Rest; 73 +/- 3 beats/min), and 3) HR fixed at peak exercise rate (DOO-Ex; 107 +/- 4 beats/min). During control exercise (DDD mode), mean arterial pressure (MAP) increased by 25 mmHg with no change in stroke volume (SV) or systemic vascular resistance. During DOO-Rest and DOO-Ex, MAP increased (+25 and +29 mmHg, respectively) because of a SV-dependent increase in cardiac output (+1.3 and +1.8 l/min, respectively). The increase in SV during DOO-Rest utilized a combination of increased contractility and the Frank-Starling mechanism (end-diastolic volume 118-136 ml). However, during DOO-Ex, a greater left ventricular contractility (end-systolic volume 55-38 ml) mediated the increase in SV.     

Endothelin-1 receptor antagonism does not influence myocardial function in hypertensive dogs

BACKGROUND: As endothelin-1 exerts positive inotropic effects, the present study evaluated whether the hypotensive effects of the endothelin-1 receptor antagonist bosentan were partially related to a decrease in myocardial performance. METHODS: In group I, eight anaesthetized open-chest dogs with perinephritic hypertension received four cumulative doses of bosentan (B1-B4). In group II, eight animals received the same doses of bosentan after autonomic blockade. Indices of heart function were derived from the pressure-length loops obtained during vena cava occlusion. RESULTS: In group I, bosentan decreased left ventricular systolic pressure (LVSP) and mean aortic pressure (MAP) dose dependently, reaching 21% and 23% respectively at B4 (LVSP from 190 +/- 8 to 150 +/- 5 mmHg, P < 0.001; MAP from 167 +/- 7 to 128 +/- 5 mmHg, P < 0.001). These effects were only related to peripheral vasodilatation, without depression of myocardial contractility, as systemic vascular resistance dropped (from 670 +/- 83 to 446 +/- 53 mmHg mL-1 min-1 x 10(4); P < 0.05), and the end-systolic pressure-length relationship (ESPLR) remained unchanged (4.0 +/- 0.4 vs. 4.3 +/- 0.7 mmHg mm-1 kg-1). Concomitantly with pressure decline, heart rate tended to increase in this group (from 150 +/- 4 to 156 +/- 6 beats min-1). When autonomic system was blocked (group II), administration of bosentan induced similar hypotensive effects as in group I (26% and 28% reduction in LVSP and MAP respectively, P < 0.001) whereas ESPLR did not change (3.0 +/- 0.9 vs. 3.1 +/- 0.5mmHg-1 mm kg-1 ). Under these sympathetically blocked conditions, heart rate significantly fell after bosentan infusion (from 120 +/- 4 to 110 +/- 6 beats min-1, P < 0.001). CONCLUSIONS: Without influencing heart function, bosentan is an efficient and safe therapy that opens up new therapeutic perspectives in human essential hypertension.     

Autosomal dominant hypertension and brachydactyly in a Turkish kindred resembles essential hypertension

1. The aim of this study was to investigate, by use of spectral analysis, (1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME); (2) the involvement of the renin-angiotensin system in these modifications, by use of the angiotensin II AT1-receptor antagonist losartan. 2. Blockade of NO synthesis was achieved by infusion for 1 h of a low-dose (10 micrograms kg-1 min-1, i.v., n = 10) and high-dose (100 micrograms kg-1 min-1, i.v., n = 10) of L-NAME. The same treatment was applied in two further groups (2 x n = 10) after a bolus dose of losartan (10 mg kg-1, i.v.). 3. Thirty minutes after the start of the infusion of low-dose L-NAME, systolic BP (SBP) increased (+10 +/- 3 mmHg, P < 0.01), with the effect being more pronounced 5 min after the end of L-NAME administration (+20 +/- 4 mmHg, P < 0.001). With high-dose L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg, P < 0.05) and reached a maximum after 40 min (+53 +/- 4 mmHg, P < 0.001); a bradycardia was observed (60 min: -44 +/- 13 beats min-1, P < 0.01). 4. Low-dose L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2, P < 0.05), whereas the high dose of L-NAME not only increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2, P < 0.001) but also decreased the mind frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, P < 0.05) of SBP. 5. Losartan did not modify BP levels but had a tachycardic effect (+45 beats min-1). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2, P < 0.001), prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose of L-NAME. Losartan also prevented the amplification of the LF oscillations of SBP induced by L-NAME; the decrease of the MF oscillations of SBP induced by L-NAME was reinforced after losartan. 6. We conclude that the renin-angiotensin system is involved in the increase in variability of SBP in the LF range which resulted from the withdrawal of the vasodilating influence of NO. We propose that NO may counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.     

Evaluation of the degree of diabetic dysautonomy with the analysis of heart rate measured at rest with the FINAPRES system

In this work, we developped the ERK (Eckmann, Ruelle and Khamporst) method of recurrent plots to analyse Heart Rate Variability (HRV), measured by the FINAPRES system in diabetic subjects. Our aim was to search some indices that might characterize the degree of dysautonomy detected in diabetic subjects, using the Ewing tests. The idea was to analyze the recurrences of the HR to previously observed values. When a value of HR, xi measured at the j-th beat come back to an already observed value, we compare the distances between the following measures (xi + 1 to xj + 1), (xj + 2 to xj + 2)... If the distances are under a given criteria during k beats, xi is deterministic of order k. Let n1 be the number of recurrent points and nk the number of k-order deterministic points, with k = 2, 3, 4... We defined the index of determinism nk + 1/nk and the Shannon entropy of the Nk = nk-nk + 1. These indices will be correlated to the total score of the 5 Ewing tests, which represent the standard measure to evaluate the diabetic dysautonomy. Blood pressure (BP) and HR were measured during about 30 minutes using the FINAPRES system in 44 healthy subjects and 60 non-hypertensive diabetic subjects. In the diabetic subjects, the age, the body weight and systolic and diastolic BP were 56 +/- 13 years (mean +/- standard-deviation), 79 +/- 14 kg, 80 +/- 10 mmHg and 137 +/- 20 mmHg. HR was weakly correlated to age (r = 0.29; p = 0.02) and the Ewing score (r = 0.31; p = 0.01). Its standard-deviation is also weakly correlated to age (r = 0.32; p = 0.01) and to the Ewing score (r = 0.34; p = 0.01). Using the ERK method, we obtained indices which are much more correlated to the Ewing score. In particular, the ratio n2/n1 and Shannon entropy were correlated to the Ewing score with r = 0.51 and r = 0.53, respectively (p < 0.0001 in both cases). These indices are also correlated to age (r = 0.40; p = 0.003) in both cases. The ERK method give some indices which are easy to obtain (measurement of HR during a rest period) and easy to interpret. These indices are strongly linked to the dysautonomy score which required a good cooperation of the patient and a great vigilance during its execution. This method could be applied to BP to explore BP regulation in hypertensive subjects.     

Respiratory sinus dysrhythmia persists in transplanted human hearts following autonomic blockade

1. The present study was performed to test whether beat-to-beat cardiovascular control in cardiac allograft recipients resides in cholinergic and/or adrenergic nerves that are intrinsic to the heart. 2. Heart rate (HR) fluctuations synchronous with respiration during spontaneous, double tidal volume and metronome-synchronized breathing were quantified in 13 human heart transplant recipients. We also examined the effects of sequential cholinergic and beta-adrenoceptor (combined) autonomic blockade on respiratory sinus arrhythmia (RSA). We computed RSA amplitude and the correlation between respiration and changes in HR (cardiopulmonary synchronization; CPS). Group means were compared using repeated-measures analysis of variance. Transplant recipients served as their own controls. 3. In the basal state, moderate RSA amplitude and CPS were observed. During cholinergic and combined blockade, we observed no significant change in RSA amplitude, whereas CPS increased significantly during combined blockade (P < 0.05). The amplitude of RSA increased during respiration at double baseline tidal volume, but not at any of the other breathing manoeuvres (P < 0.01). In contrast, CPS increased significantly during both patterned breathing manoeuvres. No significant correlation was seen between mean right atrial pressure and RSA amplitude. In 23% of subjects with low CPS, HR oscillated with arterial pressure. These oscillations were independent of respiration. During all three patterns of respiration, a significant inverse correlation was observed between CPS and pulse pressure (r = -0.53 to -0.73). Thus, as the amplitude of pulse pressure increased, respiration accounted for a smaller percentage of HR variation. 4. In conclusion, RSA persists and the magnitude of CPS increases following combined autonomic blockade. These studies suggest that while RSA after cardiac transplantation is not cholinergically or adrenergically mediated, it may be related to mechanical stretch of the sinus node caused by changes in intrathoracic pressure and perfusion pressure.     

Glomerular haemodynamics during renal artery clamping and haemorrhage in the dog

The influence of gradual decline in renal perfusion pressure (RPP) due either to renal artery clamping (C) or to haemorrhagic hypotension (HH) was studied using micropuncture techniques in anaesthetized dogs. The decrease in renal blood flow (RBF) was more profound and set in earlier during HH than during C, where perfect autoregulation was observed down to a mean arterial blood pressure of 85 mmHg. Glomerular filtration rate (GFR) was also only slightly decreased during C, with no change in filtration fraction (FF); again, a much greater decrease in GFR with an increase in FF was seen in HH. The excretion of water, electrolytes and urea were also more decreased during HH than during C. Similar changes were seen at the single nephron (SN) level. Opposite changes were observed in arteriolar resistances: during C a decrease in total arteriolar resistance (RT) amounting to -22% at a RPP of 84 mmHg and -13% at 60 mmHg was seen, due exclusively to a drop in afferent resistance (RA), but during HH there was a significant increase in RT by +36% at RPP of 110 mmHg, +39% at 85 mmHg and +68% at 60 mmHg. This increase was mainly due to an increase in efferent resistance (RE) rather than in RA: +42 vs. +31%, respectively, at 110 mmHg and +67 vs +19% respectively, at 85 mmHg. It was not until a RPP of 60 mmHg was reached that this difference between RE and RA disappeared, being +67% for RE and +69% for RA. The ultrafiltration coefficient, Kf, did not change during C and only decreased slightly with the biggest drop in RPP during HH (2.84 microliters mmHg-1 min-1 during HH vs. 4.19 microliters mmHg-1 min-1 before HH). The SNGFR/GFR ratio remained unchanged during C but declined with decreasing RPP during HH, which probably indicates a 'redistribution' of RBF to the deeper regions of the renal cortex. In conclusion, major differences in renal function were observed between C and HH whose cause is unknown.     

Oral immunization of rabbits against Pasteurella multocida with an alginate microsphere delivery system

The effects on cardiac function of slowed frequency produced by a sinus node inhibitor (zatebradine, or UL-FS 49) were studied in the conscious rabbit under control conditions (n = 16) and after heart failure was produced by rapid atrial pacing for an average of 18.5 days (n = 8). Echocardiography was used to verify severe left ventricular (LV) dysfunction, and high-fidelity micromanometry and cardiac output measurements (Doppler echo) were performed. Echocardiographic fractional shortening was 40.3 +/- 4.1 % (SD) in controls; in heart failure it was 18.0 +/- 1.6 %, and the LV was enlarged. In controls, as heart rate (HR) was decreased from 279 beats per minute (bpm) by incremental doses of zatebradine (up to 0.75 mg/kg), maximal changes occurred when the heart reached 218 bpm with a maximum decrease of the first derivative of LV pressure (LV dP/dtmax) of 15.9 %; LV enddiastolic pressure (EDP) increased from 4.3 to 8.4 mmHg along with a significant decrease in cardiac index (CI) of 15.2 %, while LV systolic pressure (SP) was stable. In heart failure, LV dP/dtmax and CI were markedly reduced compared to controls and with reduction of HR from 257 to 221 bpm LV dP/dtmax was unchanged, LVEDP increased slightly (NS), LVSP was unchanged and CI fell by 13.5 % at the highest dose. In subgroups (control n = 9, failure n = 6), in order to eliminate the hemodynamic effects of cardiac slowing by zatebradine the sinus rate present before zatebradine was matched by atrial pacing; this procedure eliminated all hemodynamic abnormalities accompanying cardiac slowing in both groups. In conclusion, slowed HR due to a sinus node inhibitor was well tolerated in severe heart failure, and all negative hemodynamic responses in both controls and in heart failure were due entirely to a negative forcefrequency effect, without a direct depressant action of zatebradine on the myocardium.     

Effects of vasoactive intestinal polypeptide on heart rate in relation to vagal cardioacceleration in conscious dogs

OBJECTIVE: The vagal cardiac accelerator (VCA) system takes part in the nervous control of the heart rate. In the present study we tried to adduce evidence that vasoactive intestinal polypeptide (VIP) contributes to vagally induced cardioaccelerations. METHODS: The effect of VIP on heart rate and arterial blood pressure was investigated after unmasking the inherent VCA activity by blocking the sympathetic accelerator and vagal decelerator influences on heart rate in conscious dogs. RESULTS: Following intravenous administration of VIP (10 micrograms i.v.) the heart rate increased by 43.6 +/- 6.7 (28.1 +/- 4.7%), from 165.6 +/- 8.5 to 209.1 +/- 7.0 beats/min (P < 0.001) and the mean arterial blood pressure decreased by 47.5 +/- 3.2 (37.9 +/- 3.0%), from 126.6 +/- 2.6 to 79.1 +/- 4.9 mmHg (P < 0.001) (n = 11). After VCA activity was reflexly enhanced by alpha 1-adrenoceptor stimulation with methoxamine, VIP increased heart rate by 36.9 +/- 7.3 (21.5 +/- 4.6%), from 179.8 +/- 5.2 to 216.7 +/- 5.8 beats/min (P < 0.001) and decreased mean arterial pressure by 79.1 +/- 6.4 (46.7 +/- 3.5%), from 168.2 +/- 4.1 to 89.1 +/- 5.0 mmHg (P < 0.001). Hence, the VIP-induced tachycardia, expressed in relative values, shows a significant attenuation after the administration of methoxamine (P < 0.05). The increase in heart rate induced by VIP appeared to be inversely related to the prevailing VCA activity, both before (r = -0.744, P = 0.009) and after methoxamine (r = -0.689, P = 0.019). The VIP-induced tachycardia is certainly not reflexly induced by the fall in arterial pressure, because intracoronary administration of VIP (0.5 microgram i.c.) caused an appreciable increase in the heart rate by 63.7 +/- 13.0 (46.4 +/- 10.4%), from 143.0 +/- 8.1 to 208.7 +/- 12.0 beats/min (P < 0.005), whereas the mean arterial pressure only slightly changed (-7.7 +/- 2.0 mmHg) (P < 0.05) (n = 6). In addition, VIP (10 micrograms i.v.) also caused a tachycardia in vagotomized dogs with blocked beta-adrenergic and muscarinic receptors. The administration of the VIP antagonists [D-p-CI-Phe6, Leu17]-VIP (50-150 micrograms i.c.) and [Lys1, Pro2,5, Leu17]-VIP (20 micrograms i.c.) did not result in alterations in VCA activity nor did the VIP antagonists block the VCA reflex response to a rise in arterial pressure. However, none of the VIP antagonists reduced the VIP-induced tachycardia either. CONCLUSION: Vasoactive intestinal polypeptide is likely to play a part in the vagal cardiac accelerator system. However, conclusive evidence for its role as the terminal transmitter in the VCA pathway will have to wait for the availability of a specific cardiac VIP receptor antagonist.     

Disturbance of peripheral microvascular function in congestive heart failure secondary to idiopathic dilated cardiomyopathy

OBJECTIVES: Previous studies of peripheral microvascular function in human heart failure have concentrated on changes in flow, and there is little information concerning the impact of heart failure on the principal determinants of transcapillary fluid exchange. This study investigated whether alterations in capillary pressure and microvascular fluid permeability can be detected in subjects with idiopathic dilated cardiomyopathy. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient (CFC) were measured in parallel studies of two overlapping groups of 12 non-oedematous subjects with idiopathic dilated cardiomyopathy and mild to moderate heart failure and in age- and sex-matched healthy controls. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and CFC by mercury-in-silastic strain gauge plethysmography using a modification of the technique which avoids assumptions concerning isovolumetric venous pressure. RESULTS: Following correction for differences in skin temperature, capillary pressure was lower in the subjects with heart failure (P = 0.02). Both CFC and isovolumetric venous pressure were greater in the subjects with heart failure than in controls (3.4 +/- 0.9 vs. 2.6 +/- 0.7 ml.min-1.mmHg-1.100 ml-1, P = 0.03; 27.1 +/- 8.4 vs. 17.2 +/- 7.2 mmHg, P = 0.01). CONCLUSIONS: These data suggest that factors other than changes in arterial inflow and venous outflow pressures are likely to play an important role in the disruption of microvascular homeostasis which occurs in heart failure. Changes in capillary hydraulic conductance may contribute to the pathogenesis of oedema.     

Filling and arterial pressures as determinants of RV stroke volume in the sheep fetus

Right ventricular (RV) function was investigated in nine fetal lambs (125-130 days gestation) that were instrumented with pulmonary artery electromagnetic flow sensors and vascular catheters. Control arterial CO2 and O2 tension, pH, and hematocrit values were 46.1 +/- 1.6 (SD) Torr, 20.6 +/- 1.8 Torr, 7.39 +/- 0.02, and 31 +/- 5.3%, respectively. Control values for right ventricular output (247 +/- 75 ml X min-1 X kg-1), stroke volume (SV, 1.5 +/- 0.4 ml X kg-1), right atrial pressure (3.7 +/- 1.2 mmHg), heart rate (166 +/- 18 beats X min-1), and arterial pressure (AP, 43 +/- 4 mmHg) were unchanged by administration of atropine and propranolol. Withdrawal and infusion of fetal blood with or without concomitant infusion of nitroprusside or phenylephrine produced RV function curves at low, normal, and high arterial pressures. All function curves had a steep ascending limb and a plateau. The breakpoint joining the limbs of the control curve was right atrial pressure 3.4 +/- 1.2 mmHg and SV 1.5 +/- 0.4 ml X kg-1. Increased AP shifted the breakpoint downward. Linear regression of SV on AP from 15 to 95 mmHg at right atrial pressure greater than breakpoint was SV = -0.016 ml X kg-1 mmHg-1 X AP + 2.25 ml X kg-1.     

Relationship between end-systolic aortic pressure and mean aortic pressure in adults

The mean blood pressure is an accurate estimate of the end-systolic aortic pressure in children. The aim of this study was: 1) to assess the relationship between the pressure at the incisura (PIAo) and the mean (MAoP) and pulse (PAoP) pressures of the supravalvular aorta in adults: and 2) to evaluate MAoP as an estimate of PIAo in adults. High fidelity pressure recordings were carried out in the supravalvular aorta in 17 men. The pressures were measured at rest in 10 consecutive beats and. In 6 subjects, during a Valsalva manoeuvre. At rest, PIAo was greater than the MAoP (109 +/- 17.9 versus 99.6 +/- 12.5 mmHg, p = 0.0001). There was a positive linear correlation between PIAo and MAoP (r = 0.93) and between PIAo and PAoP (r' = 0.77) whereas no correlation was observed between PIAo and heart rate, cardiac output or estimated total systemic arterial compliance. A beat-to-beat relationship was observed between PIAo and MAOP: 1) at rest in 16 of the 17 subjects and 2) in each subject who performed a Valsalva manoeuvre. Both at rest and during Valsalva, MAOP underestimated PIAo significantly, especially when PIAo was increased (p = 0.0001). The authors conclude that end-systolic supraaortic pressure is mainly related to the mean component of aortic pressure. MAOP slightly but constantly underestimated PIAo and this should lead to caution in assimilating MAOP to end-systolic aortic pressure in adults, especially in subjects with very high aortic pressures.     

Self-awareness, task failure, and disinhibition: how attentional focus affects eating

Prolonged continuous blood pressure (BP) and heart rate (HR) recordings from neonates of 35 to 42 weeks gestation were studied during and after ECMO. Data segments with significant deviation of BP were extracted for further analysis. The simultaneous changes in BP and HR were compared and the slope of the regression determined baroreflex sensitivity (BRS). Of 464 BP deviations, 98% produced curves with a negative slope consistent with the presence of a baroreflex. The average BRS was -1.0 +/- 0.8 bpm/mmHg (mean +/- S.D.) and curves were steeper during rising BP than falling BP (-1.1 +/- 0.9 beats/min per mmHg versus -0.9 +/- 0.6, P = 0.001). The baroreflex was more sensitive during ECMO than after ECMO to both rising BP (-1.0 +/- 0.5 beats/min per mmHg versus -0.7 +/- 0.5, P = 0.004) and falling BP (-1.0 +/- 0.6 beats/min/mmHg versus -0.7 +/- 0.5, P = 0.04). HR response curves obtained during different BP fluctuations on the same recording had varying threshold, consistent with acute resetting. One infant demonstrated chronic baroreceptor resetting over 3 days to a rise in resting BP. The near-term, critically ill neonate has an active baroreflex which is capable of resetting. ECMO was associated with accentuation of the baroreflex response.     

Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvant. Autonomic blockers were administered intravenously: atropine (0.5 mg/kg), atenolol (1 mg/kg), atenolol + atropine or prazosin (1 mg/kg). Eight animals were studied in each group. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423 +/- 6 vs 353 +/- 4 bpm; p < 0.001, unpaired Student's tests), systolic BP elevation (142 +/- 3 vs 127 +/- 2 mmHg; p < 0.001), pulse pressure increase (51 +/- 2 vs 41 +/- 2 mmHg, p < 0.01), cardiac hypertrophy (1.165 +/- 0.017 vs 1.006 +/- 0.012 g, p < 0.001), weight loss (-21 +/- 2 g; p < 0.001) and hyperthermia (37.8 +/- 0.1 vs 37.0 +/- 0.1 degrees C, p < 0.001). The intrinsic HR observed after double blockade (atenolol + atropine) was markedly increased after treatment with thyroxine (497 +/- 16 vs 373 +/- 10 bpm, p < 0.05). Vagal tone (difference between HR obtained after atenolol and intrinsic HR) was positively linearly related to intrinsic HR (r = 0.84; p < 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyrodism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (analyses on 102.4 sec segments, modulus 1.10 +/- 0.07 vs 1.41 +/- 0.06 mmHg; p < 0.01). Prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in experimental hyperthyroidism. Increased intrinsic HR resulting from the direct effect of thyroid hormone on the sinoatrial node is the main determinant of a tachycardia leading to a subsequent rise in cardiac output. The resulting BP elevation could reflexly induce a vagal activation and a sympathetic (vascular and cardiac) inhibition.     

Hemodynamic and norepinephrine responses to pacing-induced heart failure in conscious sinoaortic-denervated dogs

The present study was undertaken to determine the effects of chronic sinoaortic (baroreceptor) denervation (SAD) on the hemodynamic and sympathetic alterations that occur in the pacing-induced model of congestive heart failure. Two groups of dogs were examined: intact (n = 9) and SAD (n = 9). Both groups of dogs were studied in the control (prepace) state and each week after the initiation of ventricular pacing at 250 beats/min. After the pacemaker was turned off, hemodynamic and plasma norepinephrine levels returned toward control levels in the prepaced state and after 1 and 2 wk of pacing. However, by 3 wk all hemodynamic and norepinephrine levels remained relatively constant over the 10-min observation period with the pacemaker off. With the pacemaker off, left ventricular end-diastolic pressure went from 2.7 +/- 1.4 (SE) mmHg during the prepace state to 23.2 +/- 2.9 mmHg in the heart failure state in intact dogs (P < 0.01). Left ventricular end-diastolic pressure increased to 27.1 +/- 2.2 mmHg from a control level of 4.2 +/- 1.9 mmHg i SAD dogs (P < 0.0003). Mean arterial pressure significantly decreased in intact and SAD dogs. Resting heart rate was significantly higher in SAD dogs and increased to 135.8 +/- 8.9 beats/min in intact dogs and 136.1 +/- 6.5 beats/min in SAD dogs. There were no significant differences in the hemodynamic parameters between intact and SAD dogs after pacing. Plasma norepinephrine was significantly lower in intact than in SAD dogs before pacing (197.7 +/- 21.6 vs. 320.6 +/- 26.6 pg/ml; P < 0.005). In the heart failure state, plasma norepinephrine increased significantly in both intact (598.3 +/- 44.2 pg/ml) and SAD (644.0 +/- 64.6 pg/ml) groups. There were no differences in the severity or the magnitude of the developed heart failure state in SAD vs. intact dogs. We conclude from these date that the arterial baroreflex is not the sole mechanism for the increase in sympathetic drive in heart failure.     

Effects of aerobic exercise training and yoga on the baroreflex in healthy elderly persons

It is unclear whether the age-associated reduction in baroreflex sensitivity is modifiable by exercise training. The effects of aerobic exercise training and yoga, a non-aerobic control intervention, on the baroreflex of elderly persons was determined. Baroreflex sensitivity was quantified by the alpha-index, at high frequency (HF; 0.15-0.35 Hz, reflecting parasympathetic activity) and mid-frequency (MF; 0.05-0.15 Hz, reflecting sympathetic activity as well), derived from spectral and cross-spectral analysis of spontaneous fluctuations in heart rate and blood pressure. Twenty-six (10 women) sedentary, healthy, normotensive elderly (mean 68 years, range 62-81 years) subjects were studied. Fourteen (4 women) of the sedentary elderly subjects completed 6 weeks of aerobic training, while the other 12 (6 women) subjects completed 6 weeks of yoga. Heart rate decreased following yoga (69 +/- 8 vs. 61 +/- 7 min-1, P < 0.05) but not aerobic training (66 +/- 8 vs. 63 +/- 9 min-1, P = 0.29). VO2 max increased by 11% following yoga (P < 0.01) and by 24% following aerobic training (P < 0.01). No significant change in alpha MF (6.5 +/- 3.5 vs. 6.2 +/- 3.0 ms mmHg-1, P = 0.69) or alpha HF (8.5 +/- 4.7 vs. 8.9 +/- 3.5 ms mmHg-1, P = 0.65) occurred after aerobic training. Following yoga, alpha HF (8.0 +/- 3.6 vs. 11.5 +/- 5.2 ms mmHg-1, P < 0.01) but not alpha MF (6.5 +/- 3.0 vs. 7.6 +/- 2.8 ms mmHg-1, P = 0.29) increased. Short-duration aerobic training does not modify the alpha-index at alpha MF or alpha HF in healthy normotensive elderly subjects. alpha HF but not alpha MF increased following yoga, suggesting that these parameters are measuring distinct aspects of the baroreflex that are separately modifiable.     

Central interaction between carotid baroreceptors and skeletal muscle receptors inhibits sympathoexcitation

To determine the potential of an inhibitory interaction between the carotid sinus baroreflex (CSB) and the exercise pressor reflex (EPR), both pathways were activated to produce sympathoexcitation. It was hypothesized that, under conditions when the baroreflex increased sympathetic outflow, the interaction between CSB and EPR would be inhibitory. Bilateral carotid occlusion (BCO), electrically induced muscle contraction (EMC), and passive muscle stretch (PMS) were used to evoke sympathoexcitation. BCO decreased sinus pressure 50 +/- 5 mmHg, and the levels of muscle tension generated by EMC and PMS were 7 +/- 2 and 8 +/- 1 kg, respectively. This resulted in significant increases in mean arterial pressure (MAP) of 55 +/- 9, 50 +/- 7, and 50 +/- 6 mmHg (P = not significant, BCO vs. EMC vs. PMS) and in heart rate (HR) of 7 +/- 2, 19 +/- 4, and 17 +/- 2 beats/min (P < 0. 05, BCO vs. EMC and PMS). When BCO was combined with EMC or PMS, the reflex increase in MAP was augmented (80 +/- 8 and 79 +/- 10 mmHg; BCO+EMC and BCO+PMS, respectively; P < 0.05). However, summation of the individual MAP responses was greater than the response evoked during coactivation (106 +/- 11 and 103 +/- 12 mmHg, respectively, P < 0.05). Because summing the individual blood pressure responses exceeded the response during coactivation, the net effect was that the CSB and EPR interacted in an occlusive manner. In contrast, summation of the individual chronotropic responses was the same as the response evoked during coactivation. Moreover, there was no difference in summation of the individual MAP or HR responses when muscle afferents were activated by either EMC or PMS. In conclusion, the interaction between the CSB and the EPR in control of MAP was occlusive when both reflexes were stimulated to evoke sympathoexcitation. However, summation of the reflex changes in HR was simply additive.     

A population-based prospective evaluation of risk of sudden cardiac death after operation for common congenital heart defects

1. Ischaemic cardiac preconditioning represents an important cardioprotective mechanism which limits myocardial ischaemic damage. The aim of this investigation was to assess the impact of dichloroacetate (DCA), a pyruvate dehydrogenase complex activator, on preconditioning. 2. Rat isolated hearts were perfused by use of the Langendorff technique, and were subjected to either preconditioning (3 x 4 or 3 x 6 min ischaemia) or continuous perfusion, followed by 30 min global ischaemia and 60 min reperfusion. DCA (3 mM) was either given throughout the protocol (pretreatment), during reperfusion only (post-treatment), or not at all. Throughout reperfusion mechanical performance was assessed as the rate-pressure product (RPP: left ventricular developed pressure x heart rate). 3. In non-preconditioned control hearts, mechanical performance was substantially (P < 0.001) depressed on reperfusion (the RPP after 60 min of reperfusion (RPP(t=60)) was 4,246+/-974 mmHg beats min(-1) compared to baseline value of 21,297+/-1,728 mmHg beats min(-1)). Preconditioning with either 3 x 4 min or 3 x 6 min cycles caused significant protection, as shown by enhanced recovery (RPP(t=60) = 7,818+/-1,138, P < 0.05, and 11,123+/-587 mmHg beats min(-1), P < 0.001, respectively). 4. Addition of DCA (3 mM) to hearts under baseline conditions significantly (P < 0.001) enhanced systolic function with an increased left ventricular developed pressure of 108+/-5 mmHg compared to 88.3+/-3.0 mmHg in the controls. 5. Pretreatment with 3 mM DCA had no effect on recovery of mechanical performance in the non-preconditioned hearts (RPP(t=60) = 3,640+/-1,235 mmHg beats min(-1)) while the beneficial effects of preconditioning were reduced in the preconditioned hearts (3 x 4 min: RPP(t=60) = 2,919+/-1,060 mmHg beats min(-1); 3 x 6 min: RPP(t=60) = 8,032+/-1,367 mmHg beats min(-1)). Therefore, DCA had increased the threshold for preconditioning. 6. By contrast, post-treatment of hearts with 3 mM DCA substantially improved recovery on reperfusion in all groups (RPP(t=60) = 5,827+/-1,328 (non-preconditioned), 14,022+/-3,743 (3 x 4 min; P < 0.01) and 23,219+/-1,374 (3 x 6 min; P < 0.001) mmHg beats min(-1)). 7. The results of the present investigation clearly show that pretreatment with DCA enhances baseline cardiac mechanical performance but increases the threshold for cardiac preconditioning. However, post-treatment with DCA substantially augments the beneficial effects of preconditioning.     

Protective effects of halothane but not isoflurane against global ischaemic injury in the isolated working rat heart

The effects of equi-anaesthetic concentrations of halothane (HAL) and isoflurane (ISO) on myocardial performance, perfusion, oxygenation and lactate release were studied before, during and after a low-flow, global ischaemic insult in isolated, paced rat left heart preparations. An antegrade perfusion technique was used, where left atrial pressure (LAP) and mean aortic pressure (MAP) could be altered independently of each other. Aortic flow, coronary flow (CF) and PO2 in venous coronary effluent were continuously recorded and stroke volume, myocardial oxygen consumption (MVO2) and myocardial oxygen extraction as well as lactate release were calculated. The hearts were exposed for at least ten minutes to the perfusate without (control, n = 10) or with HAL (n = 10) or ISO (n = 10) at a MAP of 80 mmHg (10.4 kPa) and a LAP of 7.5 mmHg (1.0 kPa). After baseline measurements, MAP was reduced to 25 mmHg (3,2 kPa) for a total of nine minutes. Thereafter MAP was increased to 80 mmHg (10.4 kPa) for another nine minute period. During the whole experimental procedure, LAP was maintained at 7.5 mmHg (1.0 kPa) and heart rate at 325 beats per minute. In the pre-ischaemic control period, MVO2 was lower with HAL compared to ISO (P < 0.05) and control (P < 0.05). Stroke volume was also lower with HAL compared to control (P < 0.05). During hypoperfusion, lactate release was twice as high in the control group (P < 0.01) and with ISO (P < 0.01) compared to HAL.(ABSTRACT TRUNCATED AT 250 WORDS)