Abstract P193: Effect Of Nitroglycerin And Sympathetic Withdrawal On Splanchnic Capacitance And Cardiac Blood Volumes

The splanchnic vasculature is the largest blood volume reservoir in the human body. Reduced capacitance of this vascular bed, in part due to sympathetic venoconstriction, is proposed to play a role in hypertension and heart failure. Thus, interventions that increase splanchnic capacitance or decrease sympathetic activity may be beneficial in these conditions. In a proof-of-concept study in healthy and hypertensive subjects, we evaluated whether venodilation with nitroglycerin (NTG; Study 1) or sympathetic withdrawal with trimethaphan (Study 2) increase splanchnic capacitance and reduce cardiac and stroke volumes. In Study 1 (n=10, 36±4 yrs, BMI 26.1±1.7, 4 men), abdominal and chest scintigrams, to measure regional blood volumes, were obtained before and after 0.6 mg sublingual NTG. Splanchnic capacitance (volume-pressure relationships, VPR) and compliance (VPR slope) were estimated by recording abdominal scintigrams during progressive escalation of intrathoracic pressure using continuous positive airway pressure (CPAP) at 0, 4, 8, 12, and 16 cm H 2 O, each for ≤2 min. We found that NTG increased splanchnic blood volume at rest (4%, IQR 1.81-9.95; P<0.01) resulting in a rightward parallel shift in splanchnic VPR (P slope =0.46 and P intercept =0.01), indicating an increase in splanchnic capacitance. This was associated with a decrease in cardiac blood volume (-9%, IQR 2.2-10.3; P<0.01). In Study 2, we measured blood pressure (BP) and stroke volume, used as a surrogate of venous return, during the same CPAP protocol before and during autonomic blockade with trimethaphan in 12 hypertensive subjects (49±2 yrs, BMI 29.9±1.7, 5 men). Sympathetic withdrawal decreased systolic BP (-27±14 mmHg) and produced a leftward parallel shift in VPR (i.e. reduced stroke volume; P slope =0.12 and P intercept <0.01), indicating a reduction in venous return likely due to an increase in splanchnic capacitance. In conclusion, venodilation with NTG increased splanchnic capacitance and decreased cardiac volume. Sympathetic withdrawal had similar hemodynamic effects. These findings highlight the importance of splanchnic capacitance in cardiovascular regulation.

Maintained barostatic regulation of heart rate in digesting snakes (Boa constrictor)

When snakes digest large meals, heart rate is accelerated by withdrawal of vagal tone and an increased non-adrenergic-non-cholinergic tone that seems to stem from circulating blood-borne factors exerting positive chronotropic effects. To investigate whether this tonic elevation of heart rate impairs the ability for autonomic regulation of heart during digestion, we characterised heart rate responses to pharmacological manipulation of blood pressure in the snake Boa constrictor through serial injections of sodium nitroprusside and phenylephrine. Both fasting and digesting snakes responded with a robust tachycardia to hypotension induced by sodium nitroprusside, with digesting snakes attaining higher maximal heart rates than fasting snakes. Both fasting and digesting snakes exhibited small reductions of the cardiac chronotropic response to hypertension, induced by injection of phenylephrine. All heart rate changes were abolished by autonomic blockade with the combination of atropine and propranolol. The digesting snakes retained the capacity for compensatory heart rate responses to hypotension, despite their higher resting values, and the upward shift of the barostatic response curve enable snakes to maintain the cardiac limb for blood pressure regulation.

Diagnostics of coupling between low-frequency loops in cardiovascular autonomic control in adults, newborns and mathematical model using cross-recurrence analysis

The aim of study is to investigate effectiveness of cross-recurrence analysis for the detection of coupling between the loops of heart rate and vessel tone sympathetic control. The cross-recurrence analysis is applied to the interbeat intervals and photopletysmographic signals from the mathematical model of cardiovascular system and from adults and newborn children. The model is examined under the conditions of the four experiments: with fully operational autonomic control, autonomic control weakened by 40%, autonomic control weakened by 70% and autonomic blockade. The coupling is most pronounced in adult subjects and the model with fully operational autonomic control, while it is absent under the autonomic blockade. Autonomic control is also not fully developed in newborn children. As the result, smaller coupling strength is expected. The results of cross-recurrence analysis of the model and experimental data are compared with the results of coupling detection based on the analysos of phase synchronization. Synchronization index demonstrates good correlation with the coupling strength in the model and weak coupling in newborn children in relation to adult subjects. In both cases, no correlation is observed between the synchronization index and the results of cross-recurrence analysis.

P4423Extreme bradycardia in athletes is due to intrinsic changes within the heart

Background It is well known that athletes and in particular endurance athletes have lower resting heart rates than non-athletes. This has generally been considered a healthy adaptation. Traditionally this was thought be due to increased vagal tone. Several studies have shown that endurance athletes continue to have lower heart rates in the absence of autonomic influence suggesting bradycardia is due to intrinsic changes within the heart. A subset of endurance athletes have very low heart rates with Tour de France cyclists having described heart rates in the 30s. It is unclear whether in these elite athletes with very low heart rates the profound bradycardia is due to autonomic influence or intrinsic changes within the heart. Aim The aim of this study was to determine if extreme bradycardia in athletes is due to excess vagal tone or more profound intrinsic changes within the heart. Methods We recruited three cohorts for this study: non-athlete controls (NA), endurance athletes with a documented resting heart rate >40 (EA) and endurance athletes with a resting heart rate <40 (BA). All participants underwent baseline testing including ECG, echocardiography and VO2 max testing. All participants came back on a second occasion for treatment with dual autonomic blockade (DAB) to determine intrinsic heart rate in the following manner. After resting supine for five minutes resting heart rate was measured. Participants were then administered 0.04mg/kg of intravenous atropine. After five minutes participants were then administered 0.05mg/kg of intravenous metoprolol. This was repeated every five minutes until there was no further drop in heart rate or 0.2mg/kg had been administered. The resting heart rate at this stage was recorded as the intrinsic heart rate. Parasympathetic blockade was confirmed by lack of response to Valsalva manoeuvre and sympathetic blockade was confirmed by lack of response to metoprolol. VO2 max testing was then performed to determine maximum heart rate. Results 9 NA (7 male), 10 EA (8 male) and 5 BA (4 male) participated in this study. The average age was similar in all groups (NA 32.9y, EA 32.4y, BA 31.4y). The average resting heart rate was 71.7 in the NA group, 48.3 in the EA group and 41.6 in the BA group (p<0.05 for comparisons between all three groups). Following dual autonomic blockade resting heart rate was 86.0 in the NA group, 76.9 in the EA group and 64.4 in the BA group (p<0.05 for comparisons between all three groups). Maximum heart rate under DAB was 140.1 in the NA group, 138.0 in the EA group and 140.4 in the BA group. These differences were not significant. Conclusion In athletes with very low heart rates, bradycardia is due to more profound intrinsic changes within the heart. Acknowledgement/Funding NHMRC Project Grant

Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study

We performed the first analysis of heart rate variability (HRV) at rest and during exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that between rest and exercise there would be 1) no differences in total power (PTOT) under parasympathetic blockade, 2) a PTOT fall under β1-sympathetic blockade, and 3) no differences in PTOT under blockade of both autonomic nervous system branches. Seven men [24 (3) yr, mean (SD)] performed 5-min cycling (80 W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol, and atropine + metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity was determined by the sequence method. At rest, PTOT and the powers of low- and high-frequency components of HRV (LF and HF, respectively) were dramatically decreased with atropine and double blockade compared with control and metoprolol, with no effects on LF-to-HF ratio and on the normalized LF (LFnu) and HF (HFnu). During exercise, patterns were the same as at rest. Comparing exercise with rest, PTOT varied as hypothesized. For systolic and diastolic blood pressure, resting PTOT was the same in all conditions. During exercise, in all conditions, PTOT was lower than in control. Baroreflex sensitivity decreased under atropine and double blockade at rest and under control and metoprolol during exercise. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise. NEW & NOTEWORTHY This study provides the first demonstration, by systematic analysis of heart rate variability at rest and during exercise under full autonomic blockade on the same subjects, that suppression of vagal activity is responsible for the disappearance of spontaneous heart rate variability during exercise. This finding supports previous hypotheses on the role of vagal withdrawal in the control of the rapid cardiovascular response at exercise onset.

EPIDURAL MORPHINE IN PEDIATRIC ONCOLOGIC SURGERY

Epidural administration of opioids effectively prevents the sensitization of nociceptive neurons of the posterior horn of the spinal cord, induced by surgical trauma, without the development of motor and autonomic blockade. Study includes 52 patients aged 1 month to 18 years with malignant tumors who underwent surgical treatment at the Pediatric Oncology and Hematology Research Institute, during 2009-2016 years. Surgeries were combined (thoraco-laparotomy). The method of epidural use of morphine in pediatric oncosurgery is presented.