Ventricular Mechanical Energy Research Articles

Influence of myocardial oxygen demand on the coronary vascular response to arterial blood gas changes in humans.

It remains unclear if the human coronary vasculature is inherently sensitive to changes in arterial Po2 and Pco2 or if coronary vascular responses are the result of concomitant increases in myocardial O2 consumption/demand ([Formula: see text]). We hypothesized that the coronary vascular response to Po2 and Pco2 would be attenuated in healthy men when [Formula: see text] was attenuated with β1-adrenergic receptor blockade. Healthy men (age: 25 ± 1 yr, n = 11) received intravenous esmolol (β1-adrenergic receptor antagonist) or volume-matched saline in a double-blind, randomized crossover study and were exposed to poikilocapnic hypoxia, isocapnic hypoxia, and hypercapnic hypoxia. Measurements made at baseline and after 5 min of steady state at each gas manipulation included left anterior descending coronary blood velocity (LADV; Doppler echocardiography), heart rate, and arterial blood pressure. LADV values at the end of each hypoxic condition were compared between esmolol and placebo. The rate-pressure product (RPP) and left ventricular mechanical energy (MELV) were calculated as indexes of [Formula: see text]. All gas manipulations augmented RPP, MELV, and LADV, but only RPP and MELV were attenuated (4-18%) after β1-adrenergic receptor blockade ( P < 0.05). Despite attenuated RPP and MELV responses, β1-adrenergic receptor blockade did not attenuate the mean LADV vasodilatory response compared with placebo during poikilocapnic hypoxia (29.4 ± 2.2 vs. 27.3 ± 1.6 cm/s) and isocapnic hypoxia (29.5 ± 1.5 vs. 30.3 ± 2.2 cm/s). Hypercapnic hypoxia elicited a feedforward coronary dilation that was blocked by β1-adrenergic receptor blockade. These results indicate a direct influence of arterial Po2 on coronary vascular regulation that is independent of [Formula: see text]. NEW & NOTEWORTHY In humans, arterial hypoxemia led to an increase in epicardial coronary artery blood velocity. β1-Adrenergic receptor blockade did not diminish the hypoxemic coronary response despite reduced myocardial O2 demand. These data indicate hypoxemia can regulate coronary blood flow independent of myocardial O2 consumption. A plateau in the mean left anterior descending coronary artery blood velocity-rate-pressure product relationship suggested β1-adrenergic receptor-mediated, feedforward epicardial coronary artery dilation. In addition, we observed a synergistic effect of Po2 and Pco2 during hypercapnic hypoxia.

The effects of graded changes in oxygen and carbon dioxide tension on coronary blood velocity independent of myocardial energy demand.

In humans, coronary blood flow is tightly regulated by microvessels within the myocardium to match myocardial energy demand. However, evidence regarding inherent sensitivity of the microvessels to changes in arterial partial pressure of carbon dioxide and oxygen is conflicting because of the accompanied changes in myocardial energy requirements. This study aimed to investigate the changes in coronary blood velocity while manipulating partial pressures of end-tidal CO2 (Petco2) and O2 (Peto2). It was hypothesized that an increase in Petco2 (hypercapnia) or decrease in Peto2 (hypoxia) would result in a significant increase in mean blood velocity in the left anterior descending artery (LADVmean) due to an increase in both blood gases and energy demand associated with the concomitant cardiovascular response. Cardiac energy demand was assessed through noninvasive measurement of the total left ventricular mechanical energy. Healthy subjects (n = 13) underwent a euoxic CO2 test (Petco2 = -8, -4, 0, +4, and +8 mmHg from baseline) and an isocapnic hypoxia test (Peto2 = 64, 52, and 45 mmHg). LADVmean was assessed using transthoracic Doppler echocardiography. Hypercapnia evoked a 34.6 ± 8.5% (mean ± SE; P < 0.01) increase in mean LADVmean, whereas hypoxia increased LADVmean by 51.4 ± 8.8% (P < 0.05). Multiple stepwise regressions revealed that both mechanical energy and changes in arterial blood gases are important contributors to the observed changes in LADVmean (P < 0.01). In summary, regulation of the coronary vasculature in humans is mediated by metabolic changes within the heart and an inherent sensitivity to arterial blood gases.

Oxygen-wasting effect of inotropy in the "virtual work model".

In the "virtual work model," left ventricular total mechanical energy (TME) is linearly related to myocardial oxygen consumption (MVO2). This relationship (MVO2-TME) is supposedly independent of inotropic stimulation, vascular loading, and heart rate variations. We reexamined the effect of inotropic stimulation (dopamine) on the metabolic to mechanical energy transfer in nine open-chest anesthetized pigs. Left ventricular mechanical energy was calculated using TME (mean ejection pressure x end-diastolic volume + stroke work), TMEW (end-diastolic volume reduced by unstressed ventricular volume), and the pressure-volume area (PVA). A highly linear relationship between MVO2 and mechanical energy was found for all three indexes during control and dopamine runs (r = 0.87-0.99). The slopes were unaltered by dopamine. y-Axis intercepts were (control vs. dopamine) as follows (in J. beat-1. 100 mg-1; means +/- SD): TME, 0.36 +/- 0.12 vs. 0.61 +/- 0.30 (P < 0.02); TMEW, 0.43 +/- 0.16 vs. 0.72 +/- 0.32 (P < 0.02); and PVA, 0.34 +/- 0.13 vs. 0.60 +/- 0.30 (P < 0.02). We conclude that the virtual work model is dependent on inotropic stimulation and that new insight into myocardial chemomechanical coupling is not added by this concept.

Left Ventricular QRS Widening Decreases Emax without Lowering VO2-PVA Relation in Dog Hearts.

We observed a few rare spontaneous cases of a suddenly widened QRS wave of left ventricular ECG associated with a simultaneous decrease in left ventricular (LV) contractility (Emax, end-systolic pressure-volume ratio) in excised cross-circulated dog heart experiments. The decreased Emax was not associated with a descent of the relation between cardiac oxygen consumption (VO2) and LV systolic pressure-volume area (PVA, a measure of total ventricular mechanical energy). This result is intriguing because ventricular VO2-PVA relation generally changes its elevation in proportion to Emax under various inotropic interventions. We suspected the unusual observation to reflect no change in myocardial contractility despite ventricular asynchrony augmented by an intraventricular conduction defect.

Recovery of oxygen utilization efficiency after global myocardial ischemia

The time required for myocardial oxygen utilization to recover from 12 minutes of warm ischemia was studied in 15 sheep. Five control animals had 42 minutes of cardiopulmonary bypass at 37 °C with the heart beating and vented. In 10 experimental animals, the aorta was clamped for 12 minutes during bypass with the heart vented, and the animals were perfused 30 additional minutes after removal of the clamp. In both groups, measurements of left ventricular coronary arterial blood flow, oxygen consumption (LVO 2), peak systolic pressure, circumferential systolic stress integral (CSI), and pressure volume area (PVA) were made 30 minutes after and hourly for 5 more hours after cardiopulmonary bypass ended. Reversible ischemia significantly increases the relationship between LVO 2/PVA and LVO 2/ CSI 1 hour after the clamp is released, but the relationships return to prebypass values by 2 hours. Ischemia significantly decreases end-systolic elastance, which remains depressed thereafter. Cardiopulmonary bypass without myocardial ischemia significantly decreases total ventricular mechanical energy output and oxygen utilization efficiency of the working sheep heart but does not significantly alter end-systolic elastance or the LVO 2/ PVA and LVO 2/CSI relationships. Twelve minutes of warm ischemia impairs oxygen utilization efficiency in the reperfused sheep heart for more than 60 minutes but less than 120 minutes.

Relationship between total mechanical energy and oxygen consumption in the stunned myocardium

We studied the relationship between left ventricular oxygen consumption (LVVo 2) and total ventricular mechanical energy production as determined by calculation of the systolic pressure-volume area (P-VA) before and after 25 minutes of warm ischemia in 7 sheep. We compared the relationship between LVVo 2 and P-VA with the relationships between LVVo 2 and stroke work and between LVVo 2 and the systolic stress integral. Using the methods presented, P-VA can be measured in vivo (n = 123) in both preischemic and postischemic hearts. Ischemia increases the slopes of the relationship between LVVo 2 and P-VA and between stroke work and the systolic stress integral, and reduces the oxygen utilization efficiency of stroke work to less than 2%. Coefficients of determination for the relationship between LVVo 2 and P-VA are, in general, higher than those between LVVo 2 and either stroke work or the systolic stress integral. We conclude that systolic P-VA can be measured in vivo using recently developed methods and that it is applicable to postischemic “stunned” hearts. Because P-VA and LVVo 2 can be converted into identical energy units, calculation of P-VA permits calculation of myocardial oxygen utilization efficiency.