The present study investigated the role of cardiac nerves on homeometric autoregulation in anesthetized dogs during acute volume loading. Ventricular pressure-volume loops (conductance catheter method) were constructed during acute volume loading with intact cardiac nerves (ICN) and after cardiac decentralization (DCN; bilateral ablation of thoracic vagosympathetic complexes, stellate ganglia and anterior and posterior ansae subclavia). Arterial pressure increased as expected after volume loading but no significant changes were observed for heart rate and other hemodynamic parameters. Coronary sinus venous oxygen content was also higher regardless of nerve status in response to the overall increase in cardiac work. Pressure-volume catheter data showed markedly higher end-systolic volumes after volume loading under ICN and DCN conditions; stroke volume (mL/beat) and stroke work (mL/mm Hg) were not changed but LV ejection fraction was significantly lower. End-diastolic volume and cardiac output did not change. In addition, systemic vascular resistance and tau were higher with volume loading but no differences between ICN and DCN were observed. These findings show that acute volume loading produces an immediate influence on LV function independent of cardiac nerve status.
The intrinsic cardiac nervous system regulates beat-to-beat coordination of regional cardiac function and integrates both sympathetic and parasympathetic efferent activity [
Homeometric autoregulation allows the LV to eject the same stroke volume against a wide range of resistances without increasing end-diastolic pressure and to increase contractility by reducing the duration of systole within the total cardiac cycle [
Volume overload is frequently encountered in patients with co-morbidities (chronic kidney disease, heart failure, etc.) and is associated with adverse outcomes. The present study examined whether intact cardiac nerves contribute to homeometric autoregulation in anesthetized dogs during acute volume loading. LV pressure-vol- ume loops were constructed using the conductance catheter method [
These studies were approved by the Laval University Animal Ethics Committee and were conducted in accordance with the Guide for the Care and Use of Experimental Animals (vols. 1 and 2) of the Canadian Council on Animal Care.
Healthy adult mongrel dogs of either gender, weighing 20 - 30 Kg were fasted overnight, premedicated (Atravet, 0.5 mg/Kg; IM) and then anesthetized with sodium pentobarbital (30 mg/kg, IV). Butorphanol tartrate (0.1 mg/Kg, IM) was administered for analgesia. After endotracheal intubation, dogs were ventilated with oxygen-enriched room air; respiratory rate and tidal volume were adjusted to maintain blood gases within physiological levels and atelectasis was prevented by maintaining end-expiratory pressure at 5 - 7 cm H2O. Normothermia (38˚C ± 1˚C) was maintained with a water-jacketed Micro-Temp heating blanket (Zimmer, Dover, OH) and body temperature was monitored with a temperature probe in the trachea.
In the supine position, vascular introducer sheaths (8 Fr, Terumo Medical Corp., USA) were placed in the left and right femoral arteries; a triple-lumen central venous catheter (7 Fr, Arrow-Howes™, Arrow Intl. Inc., Reading, PA) was placed in the right femoral vein for administration of drugs and fluids.
A splenectomy was done through a mid-line abdominal incision as previously described [
In the left lateral position, a thoracotomy was performed through the third and fifth intercostal spaces (4th and 5th ribs were removed to facilitate access to the extracardiac nerves). Left and right thoracic vagosympathetic complexes, left and right stellate ganglia and the anterior and posterior ansae subclavia were dissected free of surrounding tissues [
The heart was exposed and suspended in a pericardial cradle. Catheters were inserted into the left atrium, the coronary sinus (for venous pressure measurements) and the pulmonary artery (for conductance catheter calibration). A 5Fr micro-tipped pressure transducer (MPC500; Millar Instruments Inc., Houston TX) was placed in the LV cavity through the apex to measure LV pressure and its first derivative; a 7Fr Pigtail catheter was advanced to the aortic root via the left femoral artery to measure arterial pressures. A 7 Fr, 12-electrode conductance catheter (CD Leycom, Zoetermeer, The Netherlands) was advanced via the femoral artery sheath and positioned at the LV apex along the longitudinal axis of the ventricle for construction of LV pressure-volume relations (LVPVR). After all catheters were positioned, dogs were given 500 IU heparin sodium intrvenously and allowed to stabilize for 30-min.
Left atrial, ascending aorta and coronary sinus catheters were connected to Statham P23Db strain gauge manometers; zero was set at mid-chest level. Millar micro-tipped pressure transducers were cross-calibrated with systolic aortic and diastolic left atrial pressures. All data were continuously recorded and stored on computer hard drive for later off-line analysis using AxoScope data acquisition software. The conductance catheter was calibrated using the hypertonic saline technique [
Under baseline conditions (i.e. Low) with intact cardiac nerves (ICN), LVPVR (ICN-Low) was constructed by acute vena caval occlusion for ≤12-sec. After return to steady-state, 300 mL of diluted blood was infused into the left atrium over 5-min; with this intervention LV pressure increased ~30 mm Hg. Upon return to steady state conditions a second LVPVR (ICN-High) was recorded.
After the first acute volume loading step, extracardiac nerves (i.e. stellate ganglia, ansae subclaviae and vagus) were excised bilaterally. The completeness of cardiac decentralization (DCN) was confirmed by the absence of heart rate and LV dynamics during direct electrical stimulation of the left and right ansae subclaviae (10 Hz, 5 ms, 5 - 7 V) and the left and right thoracic vagi (20 Hz, 5 ms, 5 - 7 V) [
LV function data including stroke volume (SV; mL), end-diastolic (EDV; mL), end-systolic volume (ESV; mL), stroke work (SW; mL∙mm Hg) and LV ejection fraction (LVEF; %-calculated as SV/EDV) were obtained using the conductance catheter. Differences in cardiac hemodynamics, blood gases and ventricular function were asses- sed by ANOVA. All statistical analyses were carried out using SAS software (SAS Institute Inc., Cary, NC, USA).
As shown in
Arterial pressure increased as expected considering the experimental model; no change was observed for coronary sinus pressures (cf.
End-systolic volume increased markedly after volume loading under ICN and DCN conditions (cf.
Hct | PaO2 tension | PaCO2 tension | AO2 content | CSO2 content | ||||||
---|---|---|---|---|---|---|---|---|---|---|
INN | DCN | INN | DCN | INN | DCN | INN | DCN | INN | DCN | |
Low | 32 ± 5 | 31 ± 4 | 134 ± 34 | 130 ± 32 | 43 ± 8 | 45 ± 13 | 12.7 ± 1.2 | 13.2 ± 1.0 | 5.8 ± 0.4 | 6.2 ± 0.7 |
High | 30 ± 4 | 29 ± 5 | 143 ± 48 | 132 ± 36 | 43 ± 10 | 46 ± 14 | 12.2 ± 0.9 | 12.1 ± 1.0 | 4.8 ± 0.8 | 4.9 ± 0.9 |
p DCN | NS | NS | NS | NS | NS | |||||
p High | NS | NS | NS | NS | 0.03 | |||||
p Inter | NS | NS | NS | NS | NS |
Data are mean ± 1 SD. Hct (volume %): hematocrit; PaO2, PaCO2 (mm Hg): arterial oxygen, carbon dioxide tension; AO2 content, CSO2 content (mL/mL): arterial, coronary sinus oxygen content. P values were obtained from ANOVA with repeated-measures analyses; Student-Newman-Keuls multiple range test was performed on main-effect means to identify differences between interventions.
HR | PAosys | PAodias | CSPsys | CSPdias | ||||||
---|---|---|---|---|---|---|---|---|---|---|
INN | DCN | INN | DCN | INN | DCN | INN | DCN | INN | DCN | |
Low | 108 ± 14 | 104 ± 10 | 97 ± 11 | 94 ± 13 | 67 ± 8 | 65 ± 8 | 8 ± 4 | 7 ± 3 | 3 ± 1 | 3 ± 2 |
High | 107 ± 13 | 106 ± 10 | 135 ± 12 | 136 ± 12 | 90 ± 3 | 88 ± 6 | 9 ± 5 | 9 ± 5 | 4 ± 3 | 3 ± 2 |
p DCN | NS | NS | NS | NS | NS | |||||
p High | NS | 0.001 | 0.001 | NS | NS | |||||
p Inter | NS | NS | NS | NS | NS |
Data are mean ± 1 SD. HR (beats per minute): heart rate; PAosys, PAodias (mm Hg): systolic, diastolic arterial pressure; CSPsys, CSPdias (mm Hg): systolic, diastolic coronary sinus pressure. P values were obtained from ANOVA with repeated-measures analyses; Student-Newman-Keuls multiple range test was performed on main-effect means to identify differences between interventions.
ESV | EDV | CO | Tau | Ees | EF | |||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
INN | DCN | INN | DCN | INN | DCN | INN | DCN | INN | DCN | INN | DCN | |
Low | 13 ± 3 | 12 ± 6 | 24 ± 8 | 22 ± 9 | 1.02 ± 0.46 | 0.81 ± 0.35 | 33.2 ± 4.4 | 33.8 ± 5.0 | 3.7 ± 0.3 | 3.8 ± 1.0 | 41 ± 2 | 40 ± 12 |
High | 18 ± 7 | 19 ± 9 | 27 ± 10 | 28 ± 11 | 0.72 ± 0.37 | 0.71 ± 0.20 | 38.6 ± 3.7 | 41.8 ± 4.3 | 3.9 ± 1.2 | 4.1 ± 1.6 | 26 ± 8 | 28 ± 7 |
p DCN | NS | NS | NS | NS | NS | NS | ||||||
p High | 0.05 | NS | NS | 0.04 | NS | 0.002 | ||||||
p Inter | NS | NS | NS | NS | NS | NS |
Data are mean ± 1 SD. ESV, EDV (mL): end-systolic, end-diastolic volume; CO (L/min): cardiac output; Tau (ms): time constant of LV relaxation; Ees (mm Hg/mL): slope of the end-systolic LVPVR; EF (%): LV ejection fraction. P values were obtained from ANOVA with repeated-measures analyses; Student-Newman-Keuls multiple range test was performed on main-effect means to identify differences between interventions.
Adequacy of blood circulation is, for the most part, coordinated through the autonomic nervous system which innervates the heart and vascular system. Neural control mechanisms play a dominant role in the heart’s adaptive responsiveness to different stressors. The present study examined the effect of acute volume loading on left ventricular function in dogs with intact extra-cardiac nerves and after acute cardiac decentralization. In the presence of intact cardiac nerves, acute after load augmentation prolonged isovolumetric myocardial relaxation, increased arterial pressures and end-systolic ventricular volumes without changing cardiac output. Ventricular ejection fraction was also significantly lower after volume loading; the reduction in venous oxygen content suggests increased oxygen uptake in relation to cardiac work. Acute cardiac decentralization does not appear to further modulate direct effects of volume loading on LV function and suggests that the activation of non-neural factors is principally responsible for induction of early changes in LV function.
In normal subjects, neurohormonal mechanisms regulate water and sodium balance; activation of these mechanisms increases workload and can result in decreased cardiac function [
Study limitations. Certain methodological limitations for the present study are acknowledged. Dogs were ventilated using a positive-pressure respirator since tolerance to rapid infusions of electrolyte solution has been reported to be greater compared to animals breathing spontaneously [
In summary, volume overload is a complex pathologic process that presents significant diagnostic challenges. In the study reported here, we document that the effects of acute volume loading on regulation of LV function were not markedly affected by ablation of extra-cardiac nerves. Our findings suggest that non-neural factors initiate early adaptation of LV function in the setting of acute volume overload. While these findings are interesting, any attempt to extrapolate these data to chronic volume overload or other associated pathologies is speculative. Future investigations that focus on evaluation of volume loading in the presence of co-morbidities or any-cause chronic neuropathy may help to improve understanding of underlying mechanisms and development of effective treatment strategies.
This study was funded by a generous contribution from the Laboratoire expérimental de physiologie coro- narienne Paul Jalbert at the Institut universitaire de cardiologie et pneumologie-Université Laval.
There are no conflicts of interest to disclose for this study.
John G. Kingma,Denys Simard,Jacques R. Rouleau, (2016) Effect of Acute Volume Loading on LV Function after Acute Cardiac Decentralization in Anesthetized Canines. World Journal of Cardiovascular Diseases,06,81-87. doi: 10.4236/wjcd.2016.64009