skip to main content


Title: No evidence for pericardial restraint in the snapping turtle ( Chelydra serpentina ) following pharmacologically induced bradycardia at rest or during exercise
Most animals elevate cardiac output during exercise through a rise in heart rate ( f H ), whereas stroke volume (V S ) remains relatively unchanged. Cardiac pacing reveals that elevating f H alone does not alter cardiac output, which is instead largely regulated by the peripheral vasculature. In terms of myocardial oxygen demand, an increase in f H is more costly than that which would incur if V S instead were to increase. We hypothesized that f H must increase because any substantial rise in V S would be constrained by the pericardium. To investigate this hypothesis, we explored the effects of pharmacologically induced bradycardia, with ivabradine treatment, on V S at rest and during exercise in the common snapping turtle ( Chelydra serpentina) with intact or opened pericardium. We first showed that, in isolated myocardial preparations, ivabradine exerted a pronounced positive inotropic effect on atrial tissue but only minor effects on ventricle. Ivabradine reduced f H in vivo, such that exercise tachycardia was attenuated. Pulmonary and systemic V S rose in response to ivabradine. The rise in pulmonary V S largely compensated for the bradycardia at rest, leaving total pulmonary flow unchanged by ivabradine, although ivabradine reduced pulmonary blood flow during swimming (exercise × ivabradine interaction, P < 0.05). Although systemic V S increased, systemic blood flow was reduced by ivabradine both at rest and during exercise, despite ivabradine’s potential to increase cardiac contractility. Opening the pericardium had no effect on f H , V S , or blood flows before or after ivabradine, indicating that the pericardium does not constrain VS in turtles, even during pharmacologically induced bradycardia.  more » « less
Award ID(s):
1755187
NSF-PAR ID:
10326461
Author(s) / Creator(s):
; ; ;
Date Published:
Journal Name:
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
Volume:
322
Issue:
5
ISSN:
0363-6119
Page Range / eLocation ID:
R389 to R399
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Key points

    Imaging techniques such as contrast echocardiography suggest that anatomical intra‐pulmonary arteriovenous anastomoses (IPAVAs) are present at rest and are recruited to a greater extent in conditions such as exercise. IPAVAs have the potential to act as a shunt, although gas exchange methods have not demonstrated significant shunt in the normal lung.

    To evaluate this discrepancy, we compared anatomical shunt with 25‐µm microspheres to contrast echocardiography, and gas exchange shunt measured by the multiple inert gas elimination technique (MIGET).

    Intra‐pulmonary shunt measured by 25‐µm microspheres was not significantly different from gas exchange shunt determined by MIGET, suggesting that MIGET does not underestimate the gas exchange consequences of anatomical shunt.

    A positive agitated saline contrast echocardiography score was associated with anatomical shunt measured by microspheres. Agitated saline contrast echocardiography had high sensitivity but low specificity to detect a ≥1% anatomical shunt, frequently detecting small shunts inconsequential for gas exchange.

    Abstract

    The echocardiographic visualization of transpulmonary agitated saline microbubbles suggests that anatomical intra‐pulmonary arteriovenous anastomoses are recruited during exercise, in hypoxia, and when cardiac output is increased pharmacologically. However, the multiple inert gas elimination technique (MIGET) shows insignificant right‐to‐left gas exchange shunt in normal humans and canines. To evaluate this discrepancy, we measured anatomical shunt with 25‐µm microspheres and compared the results to contrast echocardiography and MIGET‐determined gas exchange shunt in nine anaesthetized, ventilated canines. Data were acquired under the following conditions: (1) at baseline, (2) 2 µg kg−1 min−1i.v.dopamine, (3) 10 µg kg−1 min−1i.v.dobutamine, and (4) following creation of an intra‐atrial shunt (in four animals). Right to left anatomical shunt was quantified by the number of 25‐µm microspheres recovered in systemic arterial blood. Ventilation–perfusion mismatch and gas exchange shunt were quantified by MIGET and cardiac output by direct Fick. Left ventricular contrast scores were assessed by agitated saline bubble counts, and separately by appearance of 25‐µm microspheres. Across all conditions, anatomical shunt measured by 25‐µm microspheres was not different from gas exchange shunt measured by MIGET (microspheres: 2.3 ± 7.4%; MIGET: 2.6 ± 6.1%,P = 0.64). Saline contrast bubble score was associated with microsphere shunt (ρ = 0.60,P < 0.001). Agitated saline contrast score had high sensitivity (100%) to detect a ≥1% shunt, but low specificity (22–48%). Gas exchange shunt by MIGET does not underestimate anatomical shunt measured using 25‐µm microspheres. Contrast echocardiography is extremely sensitive, but not specific, often detecting small anatomical shunts which are inconsequential for gas exchange.

     
    more » « less
  2. To determine whether acute exposure to moderate hypoxia alters central and peripheral fatigue and to test whether carbohydrate ingestion impacts fatigue characteristics, 12 trained runners completed three running trials lasting 1 h each at 65% of normoxic maximum oxygen uptake. The first trial was performed in normoxia [inspired O 2 fraction ([Formula: see text]) = 0.21], and the last two trials were completed in hypoxia ([Formula: see text] = 0.15). Participants ingested a placebo drink in normoxia (NORM-PLA), a placebo drink in hypoxia (HYP-PLA), or a carbohydrate solution in hypoxia (HYP-CHO). HYP conditions were randomized. Peripheral [change in potentiated quadriceps twitch force (ΔQ tw,pot )] and central [change in voluntary activation (ΔVA)] fatigue were assessed via preexercise-to-postexercise changes in magnetically evoked quadriceps twitch. In HYP, blood was drawn to determine the ratio of free-tryptophan (f-TRP) to branched-chain amino acids (BCAA). After exercise, peripheral fatigue was reduced to a similar degree in normoxia and hypoxia (ΔQ tw,pot  = −4.5 ± 1.3% and −4.0 ± 1.5% in NORM-PLA and HYP-PLA, respectively; P = 0.61). Central fatigue was present after normoxic and hypoxic exercise but to a greater degree in HYP-PLA compared with NORM-PLA (ΔVA: −4.7 ± 0.9% vs. −1.9 ± 0.7%; P < 0.01). Carbohydrate ingestion did not influence central fatigue (ΔVA in HYP-CHO: −5.7 ± 1.2%; P = 0.51 vs. HYP-PLA). After exercise, no differences were observed in the ratio of f-TRP to BCAA between HYP-PLA and HYP-CHO ( P = 0.67). Central fatigue increased during prolonged running exercise in moderate hypoxia although the ratio of f-TRP to BCAA remained unchanged. Ingesting carbohydrates while running in hypoxia did not influence fatigue development. NEW & NOTEWORTHY Hypoxic exposure influences the origin of exercise-induced fatigue and the rate of fatigue development depending on the severity of hypoxia. Our data suggest that moderate hypoxia increases central, but not peripheral, fatigue in trained runners exercising at 65% of normoxic maximum oxygen uptake. The increase in central fatigue was unaffected by carbohydrate intake and occurred although the ratio of free tryptophan to branched-chain amino acids remained unchanged. 
    more » « less
  3. Key points

    Haemoglobin affinity is an integral concept in exercise physiology that impacts oxygen uptake, delivery and consumption.

    How chronic alterations in haemoglobin affinity impact physiology is unknown.

    Using human haemoglobin variants, we demonstrate that the affinity of haemoglobin for oxygen is highly correlated with haemoglobin concentration.

    Using the Fick equation, we model how altered haemoglobin affinity and the associated haemoglobin concentration influences oxygen consumption at rest and during exercise via alterations in cardiac output and mixed‐venous.

    The combination of low oxygen affinity haemoglobin and reduced haemoglobin concentration seenin vivomay be unable to support oxygen uptake during moderate or heavy exercise.

    Abstract

    The physiological implications, with regard to exercise, of altered haemoglobin affinity for oxygen are not fully understood. Data from the Mayo Clinic Laboratories database of rare human haemoglobin variants reveal a strong inverse correlation (r = −0.82) between blood haemoglobin concentration andP50, an index of oxygen affinity [Hb = −0.3135(P50) + 23.636]. In the present study, observedP50values for high, normal and low oxygen‐affinity haemoglobin variants (13, 26 and 39 mmHg) and corresponding haemoglobin concentrations (19.5, 15.5 and 11.4 g dL−1respectively) are used to model oxygen consumption as a fraction of delivery at rest ( = 0.25 L min−1, cardiac output = 5.70 L min−1) and during exercise ( = 2.75 L min−1, cardiac output = 18.9 l min−1). With high‐affinity haemoglobin, the model shows that normal levels of oxygen consumption can be achieved at rest and during exercise at the assumed cardiac output levels, with reduced oxygen extraction both at rest (16.8% high affinityvs. 21.7% normal) and during exercise (55.8% high affinityvs. 72.2% normal). With low‐affinity haemoglobin, which predicts low haemoglobin concentration, oxygen consumption at rest can be sustained with the assumed cardiac output, with increased oxygen extraction (31.1% low affinityvs. 21.7% normal). However, exercise at 2.75 l min−1cannot be achieved with the assumed cardiac output, even with 100% oxygen extraction. In conclusion, the model indicates chronic alterations inP50associate directly with Hb concentration, highlighting that human Hb variants can serve as ‘experiments of nature’ to address fundamental hypotheses on oxygen transport and exercise.

     
    more » « less
  4. Abstract

    Pulmonary vascular distensibility (α) is a marker of the ability of the pulmonary vasculature to dilate in response to increases in cardiac output, which protects the right ventricle from excessive increases in afterload. α measured with exercise predicts clinical outcomes in pulmonary hypertension (PH) and heart failure. In this study, we aim to determine if α measured with a passive leg raise (PLR) maneuver is comparable to α with exercise. Invasive cardiopulmonary exercise testing (iCPET) was performed with hemodynamics recorded at three stages: rest, PLR and peak exercise. Four hemodynamic phenotypes were identified (2019 ECS guidelines): pulmonary arterial hypertension (PAH) (n = 10), isolated post‐capillary (Ipc‐PH) (n = 18), combined pre‐/post‐capillary PH (Cpc‐PH) (n = 15), and Control (no significant PH at rest and exercise) (n = 7). Measurements of mean pulmonary artery pressure, pulmonary artery wedge pressure, and cardiac output at each stage were used to calculate α. There was no statistical difference between α‐exercise and α‐PLR (0.87 ± 0.68 and 0.78 ± 0.47% per mmHg, respectively). The peak exercise‐ and PLR‐based calculations of α among the four hemodynamic groups were: Ipc‐PH = Ex: 0.94 ± 0.30, PLR: 1.00 ± 0.27% per mmHg; Cpc‐PH = Ex: 0.51 ± 0.15, PLR: 0.47 ± 0.18% per mmHg; PAH = Ex: 0.39 ± 0.23, PLR: 0.34 ± 0.18% per mmHg; and the Control group: Ex: 2.13 ± 0.91, PLR: 1.45 ± 0.49% per mmHg. Patients withα ≥ 0.7% per mmHg had reduced cardiovascular death and hospital admissions at 12‐month follow‐up. In conclusion, α‐PLR is feasible and may be equally predictive of clinical outcomes as α‐exercise in patients who are unable to exercise or in programs lacking iCPET facilities.

     
    more » « less
  5. Abstract

    Right ventricular (RV) failure remains a significant clinical burden particularly during the perioperative period surrounding major cardiac surgeries, such as implantation of left ventricular assist devices (LVADs), bypass procedures or valvular surgeries. Device solutions designed to support the function of the RV do not keep up with the pace of development of left‐sided solutions, leaving the RV vulnerable to acute failure in the challenging hemodynamic environments of the perioperative setting. This work describes the design of a biomimetic, soft, conformable sleeve that can be prophylactically implanted on the pulmonary artery to support RV ventricular function during major cardiac surgeries, through afterload reduction and augmentation of flow. Leveraging electrohydraulic principles, a technology is proposed that is non‐blood contacting and obviates the necessity for drivelines by virtue of being electrically powered. In addition, the integration of an adjacent is demonstrate, continuous pressure sensing module to support physiologically adaptive control schemes based on a real‐time biological signal. In vitro experiments conducted in a pulsatile flow‐loop replicating physiological flow and pressure conditions show a reduction of mean pulmonary arterial pressure of 8 mmHg (25% reduction), a reduction in peak systolic arterial pressure of up to 10 mmHg (20% reduction), and a concomitant 19% increase in diastolic pulmonary flow. Computational simulations further predict substantial augmentation of cardiac output as a result of reduced RV ventricular stress and RV dilatation.

     
    more » « less