Original Contributions Progressive Hypoxemia Limits Left Ventricular Oxygen Consumption (original) (raw)
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Progressive hypoxemia limits left ventricular oxygen consumption and contractility
Circulation Research, 1988
To study the cardiac effects of progressive hypoxemia, we measured the left ventricular end-systolic pressure-volume relation (ESPVR), myocardial oxygen consumption (MVOj), and myocardial oxygen delivery (MQOi) in eight thoracotomized dogs anesthetized with fentanyl and droperidol. We specifically looked for evidence of oxygen supply limitation of MVOj and depressed contractility (altered ESPVR) during stepwise decreases in inspired oxygen fraction. We hypothesized that the reported relation between MVOj and left ventricular pressure-volume area (PVA) may hold when inadequate MQOj determines MVOj, which then may limit PVA, manifested partly as a change in the ESPVR. Initially, as arterial oxygen saturation was decreased from 95 ± 3 % to 64 ±14%, coronary blood Bow increased so that MQo? was maintained with no change hi myocardial extraction ratio (ER,, = MV(VMQOi). During this first phase, lactate utilization, PVA, and ESPVR did not change. When oxygen saturation was further reduced, coronary blood flow rose no higher and ER_ increased, but not enough to maintain MVOj. Lactate consumption decreased and ST segments rose, signaling a change from aerobic metabolism. MVOj decrease was associated with a fall in PVA, which was due to a fall in blood pressure and a significant depression of the ESPVR. Specifically, the volume intercept of the ESPVR increased in all dogs (6.5-20.1 ml, p<0.0001), accounting for two thirds of the increase in end-systolic volume. The slope of the ESPVR decreased during hypoxia (13.3-6.1 mm Hg/ml, p<0.02), accounting for only one third of the observed increase in end-systolic volume. We believe that the evidence of anaerobic metabolism, the decrease hi PVA, and the depression of the ESPVR demonstrates onset of oxygen supply limitation of MVOj. Our data are consistent with the hypothesis that limited MVOj may limit PVA. The hypoxic volume intercept alteration of the ESPVR is different from changes hi the slope of ESPVR seen with other interventions. This may be analogous to recent observations in isolated muscle that show hypoxic depression in contractility to be different from other interventions. (Circulation Research 1988;63: 849-859) E vidence of depressed cardiac function is frequently found in patients with acute hypoxemic respiratory failure. 1 In this study, we attempted to demonstrate potential adverse effects of arterial hypoxemia on left ventricular mechanics and to quantitatively show the limit of aerobic myocardial metabolism during acute hypoxemia. Gremels and Starling 2 demonstrated that hypoxia results in a dilated, poorly contracting heart. More recent studies have demonstrated hyp-From the
Hemodynamic dependence of myocardial oxygen consumption indexes
American Journal of Physiology-Heart and Circulatory Physiology, 1990
We tested the afterload and contractile state dependency of three indexes of myocardial oxygen consumption (MVO2): total energy requirement (Et), pressure work index (PWI), and pressure-volume area (PVA). MVO2 was measured in seven isolated canine hearts at four or five different end-diastolic volumes at each of three settings of afterload resistance and with the hearts contracting isovolumically. In several hearts, contractility was also varied by dobutamine infusion. Measured MVO2 (MMVO2) was compared with values predicted (PMVO2) by each index. There was always a high degree of correlation between MMVO2 and PMVO2 for each of the indexes. However, there was a large degree of variability in the coefficients of the MMVO2-PMVO2 relation from one heart to another. We also observed a statistically significant influence of both afterload and contractile state on the predictive power of each of the indexes. Thus each index that we tested had shortcomings in being able to predict MVO2 acc...
The oxygen consumption paradox of “stunned myocardium” in dogs
Basic Research in Cardiology, 1990
The contractile state of the heart is a major determinant of myocardial oxygen consumption. Since regional myocardial contractility can be severely impaired following a transient coronary occlusion, post-ischemic myocardium is frequently assumed to consume less oxygen. To test this assumption, regional myocardial function and oxygen consumption were studicd in anesthetized dogs during 2 h of myocardial rcperfnsion following either a 15-min (Group I) or 4-h (Group I1) left anterior descending coronary artery occlusion. Both groups developed similar post-ischemic regional dysfunction characterized by paradoxical motion (negative shortening). Measured as a percent of baseline segment shortening, anterior wall function in Group I (n = 8) and Group II (n = 5) at 30 min of reperfusion was-33 _-4-11% and-34 _+ 16 % (p = NS) and at 120 min was-23-9 % and-40 + 16 % (p=NS). However, the two groups showed a marked difference in regional myocardial oxygen consumption during rcperfusion. Despite the abnormal wall motion, regional oxygen consumption in Group I at 30 and 120 min of reperfusion was unchanged from prc-ischcmic levels as measured as a percent of baseline: 104+20% (p=NS) and 111_+21% (p=NS). In contrast, regional oxygen consumption in Group II was markedly depressed from baseline at 30 and 120 min of reperfusion: 42 _+ 7 % (p < .01) and 40 _+ 8 % (p < .01). To determine whether the dissociation between regional myocardial oxygen consumption and function in Group I was related to mitoehondrial uncoupling, six additional dogs were studied. Tissue samples were obtained from post-ischemic myocardium after 120 min of reperfusion following a 15-rain coronary artery occlusion, and compared to non-ischemic myocardium. There were no differences in the in vitro mitochondrial respiratory rates or oxidative phosphorylation capacity between the post-ischemic and non-ischemic myocardinrn. Thcrefore, in the post-ischemlc myocardium, significant depressions in regional contractility may not be associated with falls in oxygen consumption. Following a 15-min coronary artery occlusion, the injured myocardium maintains a paradoxically high oxygen consumption with normal mitochondrial function despite decreased contractility and abnormal wall motion.
Right ventricular oxygen supply/demand balance in exercising dogs
American Journal of Physiology-Heart and Circulatory Physiology, 2001
This is the first investigation of right ventricular (RV) myocardial oxygen supply/demand balance in a conscious animal. A novel technique developed in our laboratory was used to collect right coronary (RC) venous blood samples from seven instrumented, conscious dogs at rest and during graded treadmill exercise. Contributions of the RV oxygen extraction reserve and the RC flow reserve to exercise-induced increases in RV oxygen demand were measured. Strenuous exercise caused a 269% increase in RV oxygen consumption. Expanded arteriovenous oxygen content difference (A-VΔO2) provided 58% of this increase in oxygen demand, and increased RC blood flow (RCBF) provided 42%. At less strenuous exercise, expanded A-VΔO2 provided 60–80% of the required oxygen, and increases in RCBF were small and driven by increased aortic pressure. RC resistance fell only at strenuous exercise after the extraction reserve had been mobilized. Thus RC resistance was unaffected by large decreases in RC venous Po...
Circulation Research, 1980
Moderate and severe levels of experimental valvular aortic stenosis (VAS) were produced in anesthetized, open-chest dogs to determine the effects of VAS on subepicardial (EPI) and subendocardial (ENDO) blood flow, O 2 extraction, and O 2 consumption (MVO 2). Regional flow was determined by microspheres, and O 2 saturation and extraction were analyzed by a three-wavelength absorbance microspectrophotometric method. Left ventricular pressure-volume work increased by 49% in moderate and 135% in severe VAS. The ENDO:EPI flow ratio averaged 1.21 ± 0.09 in controls and decreased to 0.90 ± 0.16 in moderate and 0.89 ± 0.09 in severe VAS, and coronary flow increased by 40% and 58%, respectively. O2 extraction increased with both moderate and severe VAS, with extraction being higher in the ENDO than the EPI. MVO 2 increased more in severe VAS than in moderate VAS. The ENDO: EPI MVO2 ratios fell to 1.10 (moderate) and to 0.84 (severe) from 1.44 in controls. We conclude that the O 2 supply and consequently the MVO 2 became limited in the ENDO relative to that in the EPI by simultaneous limitation of the O 2 extraction reserve and the blood flow to this region during the increased O 2 requirements imposed by experimentally induced VAS.
Functional heterogeneity of oxygen supply-consumption ratio in the heart
Cardiovascular Research, 1999
In this review, the regional heterogeneity of the oxygen supply-consumption ratio within the heart is discussed. This is an important functional parameter because it determines whether regions within the heart are normoxic or dysoxic. Although the heterogeneity of the supply side of oxygen has been primarily described by flow heterogeneity, the diffusional component of oxygen supply should not be ignored, especially at high resolution (tissue regions <1 g). Such oxygen diffusion does not seem to take place from arterioles or venules within the heart, but seems to occur between capillaries, in contrast to data recently obtained from other tissues. Oxygen diffusion may even become the primary determinant of oxygen supply during obstructed flow conditions. Studies aimed at modelling regional blood flow and oxygen consumption have demonstrated marked regional heterogeneity of oxygen consumption matched by flow heterogeneity. Direct, non-invasive indicators of the balance between oxygen supply and consumption include NADH videofluorimetry (mitochondrial energy state) and microvascular PO measurement by the Pd-porphyrin phosphorescence technique. These indicators have shown a 2 relatively homogeneous distribution during physiological conditions supporting the notion of regional matching of oxygen supply with oxygen consumption. NADH videofluorimetry, however, has demonstrated large increases in functional heterogeneity of this ratio in compromised hearts (ischemia, hypoxia, hypertrophy and endotoxemia) with specific areas, referred to as microcirculatory weak units, predisposed to showing the first signs of dysoxia. It has been suggested that these weak units show the largest relative reduction in flow (independent of absolute flow levels) during compromising conditions, with dysoxia initially developing at the venous end of the capillary.
Regression of ventricular hypertrophy abolishes cardiocyte vulnerability to acute hypoxia
The Anatomical Record, 1990
Left ventricular hypertrophy (LVH) secondary to a pressure overload commonly leads to perfusion abnormalities that may limit oxygen delivery to the myocardium and, therefore, result in cardiocyte intracellular damage. We initiated this study to test the hypothesis that the increased vulnerability of the hypertrophied left ventricle to acute hypoxia is minimized when LVH regresses and maximal coronary flow returns to normal. Six-month-old spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were divided into control or one of two antihypertensive treatment groups. A 3-month treatment consisted of captopril (75-100 mg/kg) or hydralazine (80-160 mg/L) with hydrochlorothiazide (500 mg/L) added to each therapy. At the conclusion of the treatment period, the rats were administered a 7% O2-93% N2 gas mixture for 20 minutes to induce acute hypoxic stress during which time hemodynamics, blood gases, and pH were monitored. The heart was then rapidly fixed by vascular perfusion and prepared for electron microscopy. Captopril and hydralazine were equally effective in lowering arterial pressure in both strains, but only captopril was efficacious in reducing heart mass. Hypoxia-induced changes in hemodynamics, blood gases, and pH were similar in all of the groups; PO2 was decreased by about 70%. The electron micrographs revealed that the hypertrophied left ventricle consistently showed morphologic evidence of hypoxic damage (as indicated by T-tubular swelling, intracellular edema, and mitochondrial alterations); in contrast hypoxia had little effect on the non-hypertrophied ventricle. Captopril treatment resulted in a disappearance of the lability to hypoxic damage while hydralazine caused a small reduction in the frequency of hypoxic damage. In conclusion, reversal of hypertension alone had little effect on cardiocyte vulnerability to acute hypoxia, but reversal of hypertension in conjunction with regression of LVH prevented the intracellular damage characteristic of hypoxia. Thus, LVH and its associated maximal perfusion decrement, rather than hypertension per se, underlie cardiocyte vulnerability to hypoxic stress.
Circulation, 1991
To establish whether pressure-volume areas (PVAs) calculated using the maximum time-varying elastance (Emax) have a relation with myocardial oxygen consumption (MVO2) that improves on other indexes of myocardial oxygen demand, we studied nine dogs of either sex weighing 19-39 kg, which were instrumented with a micromanometer left ventricular (LV) catheter and a Wilton-Webster coronary sinus flow catheter and had red blood cells tagged with technetium-99m for radionuclide angiography. Hemodynamics, coronary sinus flow determinations, and radionuclide angiograms were obtained under control conditions and during three to five steady-state loading conditions (mean +/- SD, 5.6 +/- 0.7). Isochronal pressure-volume data points from each pressure-volume loop were subjected to linear regression analysis to calculate Emax. The Emax relations, diastolic curves, and systolic portions of each pressure-volume loop were used to obtain calibrated PVAs. The Emax PVA (mm Hg.ml.beat-1.100 g-1) and MVO...