Search

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. [ABSTRACT FROM AUTHOR]

Muscle metaboreflex activation (MMA) during dynamic exercise induces a substantial increase in cardiac work and oxygen demand via a significant increase in heart rate, ventricular contractility and afterload. This increase in cardiac work should lead to coronary metabolic vasodilation. However, in this situation, little if any coronary vasodilation is observed. It is unclear if this lack of coronary vasodilation, which occurs as a result of increased coronary sympathetic stimulation due to MMA, suppresses any further increases in left ventricular contractility (LVC). The purpose of this study was to determine if this lack of coronary vasodilation leads to a buffered increase in LVC. Using chronically instrumented, conscious dogs we measured arterial pressure, cardiac output (CO), circumflex blood flow (CxBF), and calculated coronary vascular conductance (CVC), maximal derivative of ventricular pressure (dp/dt), and preload recruitable stroke work (PRSW) at rest and during mild exercise (2mph) before and after MMA. Experiments were repeated after alpha-1 adrenergic blockade (prazosin ∼50 μg/kg). During prazosin we observed significantly greater increases in CVC, CxBF, CO, dP/dt, and PRSW, with MMA, over that of the control condition. We conclude that the lack of coronary vasodilation limits further improvement in LVC. NIH HL 55473 [ABSTRACT FROM AUTHOR]

Underperfusion of active skeletal muscle elicits a reflex pressor response -- termed the muscle metaboreflex (MMR). In normal dogs during moderate dynamic exercise (MOD), MMR activation causes large increases in left ventricular contractility (LVC), cardiac output (CO) and mean arterial pressure (MAP) whereas in heart failure (HF), although MAP increases, the rise in CO is virtually abolished which may be due to an impaired ability to increase LVC. A widely accepted index of contractility is preload recruitable stroke work (PRSW) calculated from the stroke work-end diastolic volume relationship. The objective of the present study was to determine whether MMR increases in PRSW observed in normal dogs during MOD are abolished in HF. Conscious dogs were chronically instrumented to measure left ventricular pressure and volume at rest, during MOD with and without partial hind-limb ischemia to elicit MMR responses. In normal conditions, MMR activation increased PRSW from 107.1 ± 6 to 142.9 ± 10 mmHg (P < 0.05) and CO increased from 8.4 ± 0.5 to 9.8 ± 0.6 l/min. After induction of HF, CO and PRSW were significantly lower at rest. Although CO increased significantly from rest to exercise, MMR activation caused no significant change in either CO or PRSW. We conclude that the ability of the MMR to induce increases in LVC is abolished in HF and that the reflex increases in MAP occur solely via peripheral vasoconstriction. [ABSTRACT FROM AUTHOR]

Dynamic exercise attenuates arterial baroreflex sensitivity (BRS) in the control of heart rate (HR) during rapid, spontaneous changes in blood pressure. However the effect of muscle metaboreflex activation (MRA) on BRS in this setting is unknown. Dogs were observed at rest and during mild or moderate treadmill exercise before and after MRA (via imposed hindlimb ischemia). BRS was evaluated as the slopes of the linear relationships (LRs) between left ventricular systolic pressure and HR during spontaneous sequences of ≥ 3 consecutive beats when HR changed inversely vs. pressure. During mild exercise, these LRs (expressed as bpm/mmHg) shifted upwards with a decrease in BRS (-3.0 ± 0.4 vs. -5.2 ± 0.4, P < 0.05 vs. rest). MRA caused upward and rightward shifts of the LRs and decreases in BRS (-2.1 ± 0.1, P < 0.05 vs. mild exercise). Moderate exercise shifted LRs both upward and rightward and BRS decreased (-1.2 ± 0.1, P < 0.05 vs. MRA at mild exercise). MRA elicited further upward and rightward shifts of the LRs and reductions in BRS (-0.9 ± 0.1, P < 0.05 vs. moderate exercise). We conclude that dynamic exercise resets the arterial baroreflex to higher blood pressure and HR as exercise intensity increases. In addition, increases in exercise intensity as well as MRA attenuates spontaneous BRS. [ABSTRACT FROM AUTHOR]