Biomedical subjects

D Burkhoff

Publications and source records attributed to D Burkhoff.

At least 91 records · Page 5Linked to original sources

PubMed1995

Mechanisms of the Frank-Starling phenomena studied in intact hearts.

The impact of ventricular volume on the relationship between intracellular calcium and ventricular pressure under steady-state conditions was determined in intact ferret hearts. The results reveal major quantitative differences and minor qualitative differences between these relations and those previously measured in isolated intact and skinned cardiac muscle. The importance of these differences is discussed within the context of developing a comprehensive mechanistic theory to describe load-dependence of the intact ventricle.

Animals↗

PubMed1995

Use of explanted human hearts as a model for the study of cardiac pathophysiologic conditions.

The purpose of this paper is to describe an isolated heart model that uses human hearts to study cardiomyopathy. Techniques of organ preparation and perfusion are described that result in successful restoration of explanted human hearts to a beating condition. Native hearts of transplant recipients were placed on an isolated perfusion circuit immediately after explant. After appropriate organ and circuit preparation these hearts were restored to a functional state. Studies were done to assess the stability over time and response to inotropic stimulation. Six of seven hearts were returned to a functional condition. Left ventricular pressure generation ranged from 56 to 118 mm Hg (mean 84.8 +/- 34.11) at physiologic loading conditions. Hearts remained functional from 67 to 271 minutes (mean 152 +/- 71.7) and retained up to 70% of functional capacity after 120 minutes. Hearts performed in isovolumic and ejecting modes. Hearts had a marked response to inotrope administration not previously described. We conclude that human hearts can be reproducibly restored to a functional condition after explant from transplant recipients and can be maintained in a beating state with reasonably stable pressure generation for an extended period of time, which makes this a useful model with which to study cardiac pathophysiologic conditions. These hearts demonstrate an appropriate response to inotropes not previously observed, most likely because of improved myocardial preservation and stringent control of perfusate chemical make-up.

Adult↗

PubMed1995

Selective reduction of PVR by inhalation of a cGMP analogue in a porcine model of pulmonary hypertension.

Selective reduction of pulmonary vascular resistance (PVR) remains a therapeutic goal for the treatment of pulmonary hypertension, but current therapeutic options remain limited. Although the gas nitric oxide (NO) selectively dilates the pulmonary vascular bed, it requires special equipment for administration, has a short biologic half-life, and is potentially toxic. We hypothesized that stimulation of the NO pathway at the level of its second messenger, guanosine 3',5'-cyclic monophosphate (cGMP), by targeted pulmonary delivery of a membrane-permeable nonhydrolyzable cGMP analogue would cause selective pulmonary vasodilation. Pulmonary hypertension was induced in 21 pigs by the intravenous infusion of a thromboxane A2 analogue (9,11-dideoxy-9 alpha,11 alpha-epoxymethanoprostaglandin F2 alpha). Inhaled 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) lowered PVR in a time- and dose-dependent manner, with maximal effect achieved after 20 min. Compared with physiological saline control, 8-BrcGMP inhalation (3.0 micrograms/kg) lowered PVR by 25 +/- 3% (P < 0.01), whereas there was no significant decline in systemic vascular resistance (4 +/- 6%); mean pulmonary arterial pressure declined 13 +/- 3% (P < 0.01), whereas there was little change in mean arterial pressure; cardiac output increased 10 +/- 4% (P < 0.05). PVR did not decrease after inhalation of noncyclic 8-bromoguanosine 5'-monophosphate, indicating that stimulation of the NO-cGMP pathway beyond the level of NO results in pulmonary vasodilation independent of stimulation of purinergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗

PubMed1995

The hemodynamic basis for the cardiac effects of parathyroid hormone (PTH) and PTH-related protein.

PTH and PTH-related protein (PTHrP) have been regarded to have positive inotropic effects on the heart as well as positive chronotropic and vasodilator effects. However, inotropy due to a direct effect of these peptides has not heretofore been distinguished from an indirect inotropic effect as a result of altered heart rate or coronary flow. The aim of this study was to determine whether PTH and PTHrP have direct inotropic effects in isolated perfused rat hearts. Three groups of hearts were studied; in all groups, hearts contracted isovolumically and were perfused with a constant coronary pressure. In the control group, heart rate, coronary flow, peak pressure (LVPmax), peak rate of rise of LV pressure (dP/dtmax), and peak intracellular calcium (measured by aequorin) all increased with PTH and PTHrP in a dose-dependent manner. When heart rate was fixed by pacing in a second group of rats, PTH and PTHrP increased coronary flow, LVPmax, and dP/dtmax significantly, indicating that inotropic actions were not mediated solely by chronotropic effects. However, when heart rate was fixed by pacing and, additionally, coronary flow was held constant (by maximal prevasodilation with nitroprusside) in a third group of rats, there was no significant effect of either PTH or PTHrP on LVPmax, dP/dtmax, or peak intracellular calcium. To demonstrate the responsiveness of this latter preparation to inotropic stimulation, the beta-adrenergic agonist, isoproterenol, increased LVPmax, dP/dtmax, and peak calcium even when heart rate was fixed and vasodilation was maximal. Thus, PTH and PTHrP are inotropic agents by virtue of their influence on coronary flow and heart rate, but not by any direct effect on contractile elements in the heart.

Animals↗

PubMed1995

Assessment of right ventricular contractile state with the conductance catheter technique in the pig.

OBJECTIVE: Since the conductance catheter method has facilitated evaluation of left ventricular contractile state in both laboratory and clinical studies, the aim of this study was to determine whether the technique is similarly useful for the right ventricle. METHODS: A series of right ventricular pressure-volume loops was obtained in seven open chest pigs during transient vena caval occlusion using a 12-electrode conductance catheter. End systolic pressure-volume relationships, stroke work-end diastolic volume relationships, and dP/dt-end diastolic volume relationships were compared at control and during infusion of dobutamine and esmolol. RESULTS: Right ventricular pressure-volume loops generated with the conductance catheter were of a shape consistent with those previously reported by other volume measurement techniques, and responded to changes in inotropic state in a predictable fashion. Dobutamine shifted the three contractile relationships leftward, whereas esmolol shifted them rightward. Comparisons of stroke volume derived with the conductance catheter and with a pulmonary artery flow probe demonstrated the ability of the conductance technique to measure relative volume changes. CONCLUSIONS: The conductance catheter provides a continuous measure of right ventricular volume that was used to detect changes in right ventricular contractile state in pigs. This represents a promising and much needed method for the evaluation of right ventricular function.

Animals↗

PubMed1994

Explaining load dependence of ventricular contractile properties with a model of excitation-contraction coupling.

A theory is present which accounts for a very broad range of ventricular properties that have been noted in recent experiments. The theory is based upon a four-state biochemical scheme that accounts for the dynamic interaction between calcium, actin and myosin which includes a calcium-free force generating complex between actin and myosin. This original scheme was supplemented by incorporating two additional basic properties of cardiac muscle: length dependence of calcium binding affinity and load dependence of force generation. The biochemical scheme was used to provide the force-length-time properties of cardiac muscle which were used to construct a ventricle via a spherical geometry. In addition to being able to accurately interrelate previously measured calcium and muscle force transients, this theory was able to account for many fundamental aspects of ventricular performance including: a realistic contractility dependent curvilinearity of the end-systolic pressure-volume relationship: enhancement of contractile strength on ejecting compared to isovolumic beats; improved contractile efficiency on ejecting as compared to isovolumic beats; appropriate load-dependent changes in time to peak pressure, time constant of relaxation and duration of contraction on isovolumic and ejecting beats; realistic estimated time course of tension-dependent heat generation. The explanation for these phenomena were explored within the context of the theory and presented in detail.

Actin Cytoskeleton↗

PubMed1994

Impact of isradipine on contractile performance, metabolism, and coronary resistance studied in isolated rat hearts.

In anesthetized dogs, isradipine has been reported to induce peripheral vasodilation and increase cardiac output (CO) and myocardial contractility, whereas myocardial oxygen consumption (MVO2) decreases, suggesting that isradipine may increase overall metabolic efficiency of the ventricle of intact animals. Whether isradipine has any direct myocardial effects that could cause intrinsic increase in metabolic efficiency or whether the observation relates to favorable isradipine-induced changes in hemodynamic loading conditions is not known. Therefore, we determined the direct myocardial effects of isradipine on contractile strength and metabolic efficiency in isolated rat heart. Isolated crystalloid perfused rat hearts were instrumented for measurement of ventricular pressure, volume, and MVO2. Isradipine decreased developed pressure (DP) and MVO2 in a concentration-dependent manner; at 32 nM irradipine, both quantities were approximately 70% of their control values. Isradipine caused a downward shift of the end-systolic pressure-volume relation (ESPVR) and in the relation between ventricular work (indexed by pressure-volume area, PVA) and MVO2, indicating that for any given amount of total mechanical work performed, the rat heart consumed less O2 during administration of isradipine than under control conditions. However, the magnitude of the downward shift of this relation was nearly identical to that observed in a separate group of hearts in which we decreased contractility by decreasing the perfusate calcium concentration. Thus, isradipine does not appear to have a contractility-independent effect on myocardial efficiency.

Animals↗

PubMed1993

Ventricular stroke work and efficiency both remain nearly optimal despite altered vascular loading.

Recent clinical and animal studies have suggested that ventricular-vascular coupling normally operates at either optimal ventricular efficiency (EFF = stroke work/myocardial oxygen consumption) or stroke work (SW) and that efficiency in particular is compromised by cardiac dysfunction. These distinctions between coupling states at maximal work vs. efficiency are largely based on theoretical models. To date, there are few direct experimental data defining optimal conditions for each parameter, respectively, in the same heart or tests of whether changes from these conditions must produce significant declines in both parameters. Therefore, 10 isolated blood-perfused canine hearts were studied at varying contractilities, with the heart ejecting into a simulated three-element Windkessel model of arterial impedance. For a given inotropic state [indexed by the slope of the end-systolic pressure-volume relationship (Ees)], myocardial oxygen consumption and SW were measured over a broad range of afterload resistances. The latter was indexed by the effective arterial elastance (Ea) and ventricular-vascular interaction expressed by the ratio of Ea to Ees (Ea/Ees). On average, maximal SW occurred at Ea/Ees = 0.80 +/- 0.16, whereas EFF was maximal at Ea/Ees = 0.70 +/- 0.15 (P < 0.01). However, these differences were small, and both SW and EFF were > or = 90% of their respective optima over a broad overlapping range of Ea-to-Ees ratios (0.3-1.3, corresponds with ejection fractions ranging from approximately 40 to 80%). These data show that both SW and efficiency are nearly maximal under many conditions of ventricular-vascular interaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Impact of ejection on magnitude and time course of ventricular pressure-generating capacity.

This study focuses on elucidating how ventricular afterloading conditions affect the time course of change of left ventricular pressure (LVP) throughout the cardiac cycle, with particular emphasis on revealing specific limitations in the time-varying elastance model of ventricular dynamics. Studies were performed in eight isolated canine hearts ejecting into a simulated windkessel afterload. LVP waves measured (LVPm) during ejection were compared with those predicted (LVPpred) according to the elastance theory. LVPm exceeded LVPpred from a time point shortly after the onset of ejection to the end of the beat. The instantaneous difference between LVPm and LVPpred increased steadily as ejection proceeded and reached between 45 and 65 mmHg near end ejection. This was in large part due to an average 35-ms prolongation of the time to end systole (tes) in ejecting compared with isovolumic beats. The time constant of relaxation was decreased on ejecting beats so that, despite the marked prolongation of tes, the overall duration of ejecting contractions was not greater than that of isovolumic beats. The results demonstrate a marked ejection-mediated enhancement and prolongation of ventricular pressure-generating capacity during the ejection phase of the cardiac cycle with concomitant acceleration of relaxation. None of these factors are accounted for by the time-varying elastance theory.

Animals↗

PubMed1993

Why does pulmonary venous pressure rise after onset of LV dysfunction: a theoretical analysis.

One of the most important consequences of acute left ventricular dysfunction (LVD) is pulmonary edema resulting from a rise in pulmonary venous pressure (PVP). It is generally believed that the PVP rise is a direct hemodynamic consequence of LVD. While this paradigm seems plausible, especially if the LV is viewed as a sump pump, there is no specific evidence to support this simple explanation. A theoretical analysis was performed to assess the hemodynamic mechanisms responsible for the dramatic rise in PVP after acute LVD. The ventricles were modeled as time-varying elastances; pulmonary and systemic vascular systems were modeled as series of resistive and capacitive elements. In response to a 50% decrease in LV contractile strength [end-systolic elastance (Ees)], cardiac output (CO) and mean arterial pressure (MAP) dropped substantially, while PVP increased minimally from its baseline of 12 to approximately 15 mmHg. With LV Ees set at 50% of normal, the effects of sympathetic activation were tested. When heart rate and total peripheral resistance were increased, CO and MAP improved, yet PVP still did not rise. The only intervention that caused a substantial increase in PVP was to simulate the decrease in unstressed volume (VU) of the venous system known to occur with sympathetic activation. When VU was decreased by about 15-20% (comparable to experimentally observed shifts with acute heart failure), PVP increased above 25 mmHg. The effects of pericardial constraints were investigated, and the results suggest a major role of this organ in determining the overall hemodynamic response to acute LVD, sympathetic activation, and explaining the responses to therapy. Thus this analysis suggests that elevations of PVP do not occur simply as a direct hemodynamic consequence of acute LVD. Rather, changes in PVP may be dictated more by sympathetic control on venous capacity. If confirmed, recognition of this as a primary mechanism may prove important in directing development of new therapies and in understanding the mechanisms of disease progression in heart failure.

Animals↗

PubMed1992

Comparison between the effects of 2-3 butanedione monoxime (BDM) and calcium chloride on myocardial oxygen consumption.

The agent 2,3-butanedione monoxime (BDM) has been reported to reduce the sensitivity of myofilament force development to calcium ions, without affecting the calcium transient in myocardium. One would predict, therefore, that BDM should reduce the contractile state of the heart without reducing the amount of oxygen that is consumed to fuel the process of excitation-contraction coupling. The purpose of the present experiment was to test this hypothesis using isovolumically contracting, isolated, blood perfused canine hearts during beta-blockade induced by continuous intra-coronary infusion of propranolol (1 mg/h). Contractile state was increased in seven hearts by CaCl2 infusion. Subsequently, while the CaCl2 infusion was continued at the highest rate, contractile state was reduced by BDM infusion. At each contractile state, we measured the left-ventricular end-systolic pressure-volume relation (ESPVR), the relation between myocardial oxygen consumption and its mechanical correlate, pressure-volume area (MVO2 vs PVA), and the duration of the LV pressure waveform. Contractile state was quantified by interpolated developed pressure at a reference ventricular volume of 25 ml (P25). BDM infusion (0.5-7 mM) caused a dose-dependent reduction in contractile state (50% reduction in P25 at 2.4 +/- 0.3 mM), and a dose-independent increase in coronary blood flow. Furthermore, BDM significantly reduced the duration of the pressure waveform up to 40% at the highest rate of BDM infusion compared to the pressure waveform duration measured at maximum CaCl2 infusion. We observed a direct relationship between MVO2 of the mechanically unloaded heart and contractility; this relation was unaffected by BDM infusion (P > 0.3). The slope of the MVO2-PVA relation decreased with increases in contractile state, but this decrease was unaffected by BDM (P > or = 0.4). We conclude that in the isolated canine heart, BDM does not act energetically as expected for a myofibrillar calcium desensitizing agent.

Animals↗

PubMed1992

End-systolic pressure-volume and MVO2-pressure-volume area relations of isolated rat hearts.

We tested the utility of a standard isolated, crystalloid-perfused, isovolumic rat heart preparation for studying ventricular metabolism in terms of the myocardial oxygen consumption-pressure-volume area (MVO2-PVA) relations. The end-systolic pressure-volume relations (ESPVRs) determined between volumes of 0.15 and 0.65 ml were fit equally well by linear and nonlinear regression analysis within the data range but predicted widely differing volume-intercept (Vo) values. Linear regression analysis of the ESPVRs provided a mean slope (Ees) of 419 +/- 186 mmHg.g.ml-1 and Vo of 0 +/- 0.12 ml, respectively (n = 6). The MVO2-PVA relations were linear with a slope and MVO2 intercept of 1.30 +/- 0.31 x 10(-5) ml O2.mmHg-1.ml-1 and 0.38 +/- 0.09 x 10(-3) ml O2-beat-1.g-1, respectively. These MVO2-PVA parameters were not significantly different from those obtained when nonlinear regression analysis was applied to the ESPVR. Decreasing perfusate calcium concentration ([Ca2+]) (n = 7) resulted in a downward shift in the ESPVR, a decrease in the MVO2-PVA intercept (0.52 +/- 0.26 vs. 0.34 +/- 0.20 x 10(-3) ml O2.beat-1.g-1, P less than 0.01), and no significant change in the MVO2-PVA slope (1.33 +/- 0.47 vs. 1.57 +/- 0.69 x 10(-5) ml O2.mmHg-1.ml-1, NS). We conclude that this preparation may be a useful alternative to more expensive preparations for selected experiments in cardiac energetics.

Animals↗

PubMed1992

Effects of calcium and EMD-53998 on oxygen consumption in isolated canine hearts.

BACKGROUND: Most positive inotropic agents increase cardiac contractility by increasing the amount of Ca2+ cycled with each beat. The additional amount of oxygen that is consumed by the heart to cycle this additional Ca2+ is believed to reduce myocardial efficiency. On the other hand, it has been suggested that the agent EMD-53998 increases the Ca2+ sensitivity of the contractile proteins without affecting the intracellular Ca2+ transient in cardiac muscle. Therefore, application of this agent may increase cardiac contractility without decreasing myocardial efficiency. The purpose of the present study was to test this hypothesis. METHODS AND RESULTS: We measured myocardial oxygen consumption (MVO2) in six isolated, isovolumically beating blood-perfused canine hearts. The hearts were paced at 120 beats per minute. Contractility was varied in each heart by infusion of either CaCl2 or EMD-53998. With infusion of either agent, MVO2 was a linearly proportional function of contractility. No significant difference between CaCl2 and EMD-53998 could be detected in the interrelation between contractility and MVO2. CONCLUSIONS: We conclude that the "calcium-sensitizing agent" EMD-53998 is a potent positive inotropic agent in the isolated, blood-perfused canine heart. However, EMD-53998 does not provide an energetic advantage over currently used positive inotropic agents.

Animals↗

PubMed1992

Alterations in left ventricular mechanics, energetics, and contractile reserve in experimental heart failure.

The contributions of changes in primary systolic and diastolic properties, limitations of contractile reserve, and alterations in energy efficiency to the left ventricular dysfunction seen with chronic pacing tachycardia were investigated. Seven dogs (heart failure group) were ventricularly paced at 250 beats per minute for 26.3 +/- 2.9 days and compared with a separate control group (n = 8). STudies were performed with isolated, metabolically supported hearts coupled to a computer-controlled loading system. Pressure-volume relations and myocardial oxygen consumption (MVO2) were measured to assess chamber systolic and diastolic properties and efficiency (relation between MVO2 and pressure-volume area [PVA]). Systolic function was reduced in failure hearts versus controls as assessed by the slope of the end-systolic pressure-volume relation (1.29 +/- 0.94 versus 2.71 +/- 0.98 mm Hg/ml, p less than 0.01) and lowered end-systolic stiffness at a matched stress (956.1 +/- 123.5 versus 1,401.7 +/- 431.7 g/cm2, p less than 0.05). Diastolic chamber and myocardial stiffness were unaltered in failure hearts, but the unstressed diastolic-arrested volume was significantly larger (33.3 +/- 3.9 versus 21.9 +/- 7.6 ml, p less than 0.01). Inotropic response to increased heart rate and exogenous beta-adrenergic stimulation (dobutamine HCl) was significantly impaired in failure compared with control hearts. Most interestingly, failure hearts had a lowered slope of the MVO2-PVA relation (2.1 +/- 1.1 versus 2.9 +/- 1.4 ml O2.mm Hg-1.ml-1.100 g left ventricle-1, p less than 0.001), indicating increased efficiency of chemomechanical energy conversion. The y intercept of the MVO2-PVA relation, which reflects oxygen costs of basal metabolism and excitation-contraction coupling, was unchanged in the two groups despite decreased contractility of the heart failure hearts. These results demonstrate reduced chamber and myocardial contractility, dilatation without alteration of passive myocardial properties, impaired contractile reserve, and novel alterations in cardiac efficiency in this model of heart failure.

Animals↗

PubMed1991

Effect of a bradycardic agent on the isolated blood-perfused canine heart.

Bradycardic agents could limit the consequences of myocardial ischemia via two mechanisms: by decreasing myocardial oxygen demand (MVO2) and by increasing diastolic coronary blood flow (CBF). We investigated whether the benzazepinone UL-FS 49 affects only sinus node cells or also smooth muscle and/or myocardial cells. To avoid confounding interactions with the periphery, we performed experiments on 11 isolated, blood-perfused canine hearts. Injection of UL-FS 49 (1 mg/kg i.c.) significantly reduced heart rate (HR) from 104 +/- 7 to 93 +/- 7 min-1 (mean +/- SEM) and increased stroke volume (n = 6: 9.8 +/- 1.1 vs. 13.2 +/- 1.6 ml), so that cardiac output remained unchanged (n = 6: 1.1 +/- 0.1 vs. 1.2 +/- 0.1 l/min). The contractile state, assessed by isovolumic peak systolic pressure, was unaltered by UL-FS 49 (n = 5: 72 +/- 6 vs. 72 +/- 6 mmHg). At a constant coronary arterial pressure (CAP) of 80 mmHg, mean CBF was slightly decreased (102 +/- 11 vs. 97 +/- 10 ml/[min.100 g]) by UL-FS 49, such that mean coronary resistance remained unchanged (0.9 +/- 0.1 vs 1.0 +/- 0.1 mmHg.min.100 g/ml). The slight decreases in arteriovenous oxygen content difference (n = 6: 6.6 +/- 0.7 vs. 6.5 +/- 0.7 ml/100 ml) and in CBF lead to a calculated, significant decrease in MVO2 (n = 6: 6.9 +/- 0.5 vs. 6.0 +/- 0.4 ml.100 g/min). In conclusion, UL-FS 49 at the dose used decreases MVO2 by reducing HR in isolated canine hearts. In the absence of negative inotropic and vasodilating effects, cardiac output is maintained via increased stroke volume, and CAP will likely be preserved in situ. Thus, this specific bradycardic agent could be useful in treating ischemic myocardial disease.

Animals↗

PubMed1991

Hemodynamic consequences of ventricular interaction as assessed by model analysis.

Because of close anatomic association, the pressure and volume in one ventricle can directly influence the pressure and volume in the opposite ventricle. To examine the importance of ventricular interdependence in controlling the circulation, we developed a computer model in which ventricular interdependence could be turned on and off. Left ventricular chamber contractility, as judged by maximal elastance (Emax), was enhanced on the order of 10% as a result of ventricular interaction, whereas right ventricular Emax was affected by as much as 60% under physiological conditions. With increases in systemic vascular resistance, ventricular interaction caused a smaller stroke volume (SV) decrease than with no interaction. For canine data (SV = 21.4 ml), doubling systemic vascular resistance decreased SV by 3.7 without ventricular interdependence, 3.5 with diastolic ventricular interdependence, and 3.3 ml with diastolic and systolic ventricular interdependence. In contrast, with increases in pulmonary vascular resistance, ventricular interaction caused a greater decrease in SV than with no interaction present. Decreasing left ventricular free wall elastance or right ventricular free wall elastance decreased SV. Diastolic ventricular interdependence reduced the SV changes, whereas systolic ventricular interdependence accentuated the SV changes with alterations in right and left ventricular free-wall elastance. The results of the present simulation demonstrate the importance of ventricular interdependence in the observed responses of the right ventricle to volume overload, pressure overload, and ischemia.

Animals↗

PubMed1991

Contractile strength and mechanical efficiency of left ventricle are enhanced by physiological afterload.

Recent studies have shown that at the same endsystolic volume, ejecting beats can achieve a higher end-systolic pressure than isovolumic beats. The purpose of this study was to assess the metabolic cost, in terms of oxygen consumption (MVO2), and efficiency, in terms of the relation between MVO2 and pressure-volume area (PVA), of this increase in strength during ejection. The slope of the end-systolic pressure-volume relation (ESPVR) (Ees) was greater during ejecting than isovolumic contractions when ejection fraction (EF) was greater than approximately 30%, indicating an increase in contractile strength. The difference in Ees between the two modes of contraction was as much as 30% at EFs of 60%. In contrast, the slope of the MVO2-PVA relation was less during ejecting than isovolumic contractions, indicating a decrease in MVO2 at any given PVA. The difference in slope was as much as 20% at EFs of 60%. Thus afterload conditions, allowing substantial fiber shortening, shift the ESPVR toward greater contractile strength and increase the metabolic efficiency when viewed in terms of the relation between MVO2 and total mechanical energy generation (PVA) by the ventricle. This may reflect an energetically favorable effect of shortening on muscle force-generating capability.

Animals↗

PubMed1991

Influence of metabolic substrate on rat heart function and metabolism at different coronary flows.

The influence of metabolic substrate on contractile strength, myocardial oxygen consumption (MVO2), high- and low-energy phosphate levels, and intracellular pH were determined in isovolumically contracting isolated rat hearts perfused with solutions containing either glucose or hexanoate at both high and low coronary perfusion pressures (CPP). Contractile strength was not significantly influenced by substrate at a CPP of 80 mmHg. As coronary flow was decreased, developed pressure measured at a fixed left ventricular volume (LVV) was lower during hexanoate than glucose perfusion. The relationship between MVO2 and mechanical work determined at a CPP of 80 mmHg over a range of LVVs was shifted upward in a parallel manner when substrate was switched from glucose to hexanoate. The MVO2-work relationship measured at a fixed LVV but over a range of coronary flows (7-20 ml/min) was also parallel shifted upward on switching from glucose to hexanoate. Basal MVO2 was greater during hexanoate than glucose perfusion by an amount that accounted for two-thirds the total increase in MVO2 observed between the substrates under unloaded beating conditions. The remainder of the difference was attributed to increased energy requirements for excitation-contraction coupling. Inorganic phosphate concentrations increased more and phosphocreatine concentrations decreased more during low-flow conditions (3 ml/min) when hearts were perfused with hexanoate compared with glucose. Thus hexanoate decreases myocardial efficiency compared with glucose in large part by increasing non-work-related oxygen demands. This inefficiency impacts adversely on contractile strength and high-energy phosphate concentrations at low coronary flows.

Animals↗