The left ventricle increases contractility in response to baroreceptor unloading, which is sympathetically mediated in the anesthetized rat.

Contemporary discussion of the baroreflex includes the efferent vascular-sympathetic and cardiovagal arms. Since sympathetic postganglionic neurons also innervate the left ventricle (LV), it is often assumed that the LV produces a sympathetically mediated increase in contractility during baroreceptor unloading, but this has not been characterized using a load-independent index of contractility. We aimed to determine 1) whether LV contractility increases in response to baroreceptor unloading and 2) whether such increases are mediated via the sympathetic or parasympathetic arm of the autonomic nervous system. Ten male Wistar rats were anesthetized (urethane) and instrumented with arterial and LV pressure-volume catheters to measure mean arterial pressure (MAP) and load-independent LV contractility [maximal rate of increase in pressure adjusted to end-diastolic volume (PAdP/dtmax)], respectively. Rats were placed in a servo-controlled lower-body negative pressure (LBNP) chamber to reduce MAP by 10% for 60 s to mechanically unload baroreceptors under control conditions. LBNP was repeated in each animal following infusions of cardiac autonomic blockers using esmolol (sympathetic), atropine (parasympathetic), and esmolol + atropine. Under control conditions, PAdP/dtmax increased during baroreceptor unloading (26 ± 6 vs. 31 ± 9 mmHg·s-1·µL-1, P = 0.031). During esmolol, there was no increase in LV contractility during baroreceptor unloading (11 ± 2 vs. 12 ± 2, P = 0.125); however, during atropine, there was an increase in LV contractility during baroreceptor unloading (26 ± 6 vs. 31 ± 9, P = 0.019). During combined esmolol and atropine, there was a small increase in contractility versus control (13 ± 3 vs. 15 ± 4, P = 0.046). Our results demonstrate that, in anesthetized rats, LV contractility increases in response to baroreceptor unloading, which is largely sympathetically mediated.NEW & NOTEWORTHY This study empirically demonstrates a sympathetically mediated increase in LV contractility in response to baroreceptor unloading using a load-independent index of cardiac contractility in the anesthetized rat.

A cross-species validation of single-beat metrics of cardiac contractility.

The assessment of left ventricular (LV) contractility in animal models is useful in various experimental paradigms, yet obtaining such measures is inherently challenging and surgically invasive. In a cross-species study using small and large animals, we comprehensively tested the agreement and validity of multiple single-beat surrogate metrics of LV contractility against the field-standard metrics derived from inferior vena cava occlusion (IVCO). Fifty-six rats, 27 minipigs and 11 conscious dogs underwent LV and arterial catheterization and were assessed for a range of single-beat metrics of LV contractility. All single-beat metrics were tested for the various underlying assumptions required to be considered a valid metric of cardiac contractility, including load-independency, sensitivity to inotropic stimulation, and ability to diagnose contractile dysfunction in cardiac disease. Of all examined single-beat metrics, only LV maximal pressure normalized to end-diastolic volume (EDV), end-systolic pressure normalized to EDV, and the maximal rate of rise of the LV pressure normalized to EDV showed a moderate-to-excellent agreement with their IVCO-derived reference measure and met all the underlying assumptions required to be considered as a valid cardiac contractile metric in both rodents and large-animal models. Our findings demonstrate that single-beat metrics can be used as a valid, reliable method to quantify cardiac contractile function in basic/preclinical experiments utilizing small- and large-animal models KEY POINTS: Validating and comparing indices of cardiac contractility that avoid caval occlusion would offer considerable advantages for the field of cardiovascular physiology. We comprehensively test the underlying assumptions of multiple single-beat indices of cardiac contractility in rodents and translate these findings to pigs and conscious dogs. We show that when performing caval occlusion is unfeasible, single-beat metrics can be utilized to accurately quantify cardiac inotropic function in basic and preclinical research employing various small and large animal species. We report that maximal left-ventricular (LV)-pressure normalized to end-diastolic volume (EDV), LV end-systolic pressure normalized to EDV and the maximal rate of rise of the LV pressure waveform normalized to EDV are the best three single-beat metrics to measure cardiac inotropic function in both small- and large-animal models.

Development of a Spinal Cord Injury Model Permissive to Study the Cardiovascular Effects of Rehabilitation Approaches Designed to Induce Neuroplasticity.

As primary medical care for spinal cord injury (SCI) has improved over the last decades there are more individuals living with neurologically incomplete (vs. complete) cervical injuries. For these individuals, a number of promising therapies are being actively researched in pre-clinical settings that seek to strengthen the remaining spinal pathways with a view to improve motor function. To date, few, if any, of these interventions have been tested for their effectiveness to improve autonomic and cardiovascular (CV) function. As a first step to testing such therapies, we aimed to develop a model that has sufficient sparing of descending sympathetic pathways for these interventions to target yet induces robust CV impairment. Twenty-six Wistar rats were assigned to SCI (n = 13) or naïve (n = 13) groups. Animals were injured at the T3 spinal segment with 300 kdyn of force. Fourteen days post-SCI, left ventricular (LV) and arterial catheterization was performed to assess in vivo cardiac and hemodynamic function. Spinal cord lesion characteristics along with sparing in catecholaminergic and serotonergic projections were determined via immunohistochemistry. SCI produced a decrease in mean arterial pressure of 17 ± 3 mmHg (p < 0.001) and left ventricular contractility (end-systolic elastance) of 0.7 ± 0.1 mmHg/µL (p < 0.001). Our novel SCI model produced significant decreases in cardiac and hemodynamic function while preserving 33 ± 9% of white matter at the injury epicenter, which we believe makes it a useful pre-clinical model of SCI to study rehabilitation approaches designed to induce neuroplasticity.

Validation of a Noninvasive Assessment of Pulmonary Gas Exchange During Exercise in Hypoxia.

BACKGROUND: Pulmonary gas exchange efficiency, determined by the alveolar-to-arterial Po2 difference (A-aDo2), progressively worsens during exercise at sea-level; this response is further elevated during exercise in hypoxia. Traditionally, pulmonary gas exchange efficiency is assessed through measurements of ventilation and end-tidal gases paired with direct arterial blood gas (ABG) sampling. Because these measures have a number of caveats, particularly invasive blood sampling, the development of new approaches for the noninvasive assessment of pulmonary gas exchange is needed. RESEARCH QUESTION: Is a noninvasive method of assessing pulmonary gas exchange valid during rest and exercise in acute hypoxia? STUDY DESIGN AND METHODS: Twenty-five healthy participants (10 female) completed a staged maximal exercise test on a cycle ergometer in a hypoxic chamber (Fio2 = 0.11). Simultaneous ABGs via a radial arterial catheter and noninvasive gas-exchange measurements (AGM100) were obtained in 2-minute intervals. Noninvasive gas exchange, termed the O2 deficit, was calculated from the difference between the end-tidal and the calculated Pao2 (via pulse oximetry and corrected for the Bohr effect by using the end-tidal Pco2). Noninvasive O2 deficit was compared with the traditional alveolar to arterial oxygen difference (A-aDo2), using the traditional Riley analysis. RESULTS: Under conditions of rest at room air, hypoxic rest, and hypoxic exercise, strong correlations between the calculated gPao2 and directly measured Pao2 (R2 = 0.97; P < .001; mean bias = 1.70 mm Hg) were observed. At hypoxic rest and exercise, strong relationships between the estimated and directly measured Pao2 (R2 = 0.68; P < .001; mean bias = 1.01 mm Hg) and O2 deficit with the traditional A-aDo2 (R2 = 0.70; P < .001; mean bias = 5.24 mm Hg) remained. INTERPRETATIONS: Our findings support the use of a noninvasive measure of gas exchange during acute hypoxic exercise in heathy humans. Further studies are required to determine whether this approach can be used clinically as a tool during normoxic exercise in patients with preexisting impairments in gas exchange efficiency.

Cardiac parasympathetic activity and ventricular diastolic interactions in individuals with spinal cord injury.

STUDY DESIGN: Cohort cross-sectional study. OBJECTIVE: To investigate the relationship between cardiac vagal activity and left ventricular filling at rest and during vagal stimulation, via the cold face test (CFT), in individuals with spinal cord injury (SCI). SETTING: University-based laboratory at Brock University, St. Catharines, ON, Canada. METHODS: A total of 12 able-bodied (age: 40 ± 8.5 years) and 13 SCI individuals (age: 41 ± 8.5 years; C4-T6; AIS: A-D) were recruited. Cardiac parasympathetic activity was assessed via heart rate variability (HRV) while LV filling was assessed by conventional echocardiography. All indices of HRV and diastolic function were obtained at rest and during cardiac vagal stimulation via the CFT. RESULTS: At baseline, the able-bodied group demonstrated strong positive correlations between HRV and early diastolic filling; however, such correlations were absent in the SCI group. The CFT resulted in elevated HRV with concomitant bradycardia in the able-bodied group, while the SCI group experienced no change in HRV or heart rate during the CFT. Able-bodied individuals showed a positive correlation between the change in HRV and the change in LV diastole during the CFT, which was attributed to increased cardiac vagal tone and not the change in heart rate, however, no relationships were observed in the SCI group. CONCLUSION: In able-bodied individuals, cardiac parasympathetic activity is associated with LV filling at rest and during elevated cardiac vagal tone. After SCI, there is a discord between vagal and LV diastolic activity, where changes in autonomic function do not influence LV filling, suggesting a disconnect between parasympathetic and cardiac function.