Diabetic cardiomyopathy: an overview.
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Animals↗
Biomedical subjects
M M LeWinter
Publications and source records attributed to M M LeWinter.
Restoring forces assessed with left atrial pressure clamps.
A negative pressure (P) in the fully relaxed left ventricle (LV) indicates the presence of restoring forces generated during contraction. To assess restoring forces in the intact LV under physiological filling conditions, a servomotor system was used in anesthetized open-chest dogs (n = 8) to produce nonfilling diastoles by left atrial pressure (LAP) clamping during systole such that LAP was less than left ventricular pressure (LVP) during the subsequent diastole. Steady-state LV end-diastolic pressure (EDP) was varied by volume infusion from 4.0 +/- 1.5 (+/-SD) to 12.8 +/- 2.1 mmHg. The corresponding fully relaxed LVPs increased from -2.1 +/- 1.9 to 1.1 +/- 3.2 mmHg, P < 0.001. LAP clamping increased the rate of LVP fall by 34 +/- 28% (P < 0.001) during 10 ms after the LVP dropped below the level of the LVP-LAP crossover of the preceding normal beat. During clamped beats, two-dimensional echo revealed substantial downward displacement of the mitral valve (MV) leaflets despite the reversed LA-LV gradient and absence of filling. Thus 1) restoring forces are present at low physiological EDP but absent at high physiological EDP; 2) filling retards the rate of fall of LVP; 3) even in the absence of filling, the process of LV relaxation facilitates MV opening.
Animals↗
Effects of EMD 57033 on contraction and relaxation in isolated rabbit hearts.
BACKGROUND: Ca2+ sensitizers are reported to enhance contractility with modest effects on energy utilization. In the present study we assessed the effects of the relatively "pure" Ca2+ sensitizer EMD 57033 on mechanical performance and energy consumption in the beating heart. METHODS AND RESULTS: In 10 isolated, red blood cell-perfused rabbit hearts the effects of EMD 57033 (5.0 to 5.8 mumol/L) on left ventricular (LV) pressure and O2 consumption (VO2) were examined at heart rates of 100 and 150 beats per minute (bpm) and perfusate [Ca2+] ([Ca2+]o) of 2.5 and 1.0 mmol/L (isovolumic contractions). LV developed pressure and maximum dP/dt increased, but less so at 150 bpm or 1.0 mmol/L [Ca2+]. End-diastolic pressure also increased, more so at 150 bpm or 1.0 mmol/L [Ca2+]o. EMD 57033 decreased time to peak isovolumic pressure (Tmax) and prolonged time to 50% pressure decline (T1/2). These changes were greater at slower heart rate or lower [Ca2+]o. The magnitude of increased VO2 with EMD 57033 was greater at 100 bpm than 150 bpm but unaffected by [Ca2+]o. We then investigated the influence of ejection on the response to EMD 57033 (n = 7). The increase in developed pressure with EMD 57033 was greater for ejecting than isovolumic beats (25.5 +/- 10.2 versus 14.7 +/- 7.5 mm Hg at 100 bpm, P < .01), while the increase in end-diastolic pressure was less (P = NS). The increase in VO2 was significantly greater for ejecting than isovolumic beats (0.027 +/- 0.013 versus 0.020 +/- 0.009 mL O2/beat per 100 g at 100 bpm, P < .01). CONCLUSIONS: EMD 57033 enhances contractility and prolongs relaxation. Its effects are modulated by heart rate, [Ca2+]o, and contraction mode, with positive inotropic effects being more prominent for ejecting beats.
Animals↗
Relation between left ventricular shape and Doppler filling parameters in patients with left ventricular dysfunction secondary to coronary artery disease.
Left ventricular (LV) shape is an independent predictor of exercise capacity in patients with systolic LV dysfunction. Recent studies suggest that end-systolic LV shape is related to the generation of restoring forces during contraction that facilitate filling at lower LV pressure during subsequent diastole. To test the hypothesis that preservation of a more elliptical LV shape would be associated with a distribution of diastolic inflow characterized by increased early relative-to-late filling, 32 outpatients with coronary artery disease and ejection fraction < 40% underwent quantitative 2-dimensional and Doppler echocardiography. LV volumes, ejection fraction, and eccentricity index were measured as were standard Doppler indexes of LV filling. Simple and multiple linear regression models were used to examine relations between LV shape and Doppler measurements. LV eccentricity at end-systole correlated strongly with the Doppler atrial filling fraction (r = -0.670; p < 0.001) and the ratio of early-to-late flow velocity integrals (r = 0.648; p < 0.001). No other 2-dimensional echocardiographic variable was significantly correlated with any other Doppler index of LV filling. Thus, LV shape at end-systole appears to be an important determinant of diastolic filling patterns. In patients with systolic LV dysfunction, preservation of a more elliptical chamber is associated with a diastolic inflow pattern characterized by increased early relative-to-late diastolic filling.
Aged↗
Observations suggesting a high incidence of exercise-induced severe mitral regurgitation in patients with mild rheumatic mitral valve disease at rest.
OBJECTIVES: The aim of this study was to determine the hemodynamic effects of upright bicycle ergometry in symptomatic patients with mild, mixed mitral stenosis and regurgitation. BACKGROUND: Patients with seemingly mild rheumatic mitral valve disease often complain of exertional dyspnea or fatigue. These symptoms are usually ascribed to flow-dependent increases in the gradient across the stenotic mitral valve. Although catheterization studies in these patients may demonstrate an increase in mitral valve gradient proportional to an increase in cardiac output, this approach does not specifically address the underlying mechanism of any observed increases in mitral gradient or left atrial (i.e., pulmonary capillary wedge) pressure. Exercise echocardiography is uniquely suited to the dynamic assessment of exercise-induced hemodynamic changes. METHODS: Fourteen symptomatic patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest performed symptom-limited upright bicycle ergometry with quantitative two-dimensional, Doppler and color Doppler echocardiographic analysis. RESULTS: Average pulmonary artery systolic pressure in the 13 patients with adequate spectral signals of tricuspid regurgitation increased from 36 +/- 5 mm Hg (mean +/- SD) at rest to 63 +/- 14 mm Hg at peak exercise (p < 0.001). The mean transmitral pressure gradient in all patients increased from 4.5 +/- 1.4 mm Hg at rest to 12.7 +/- 2.7 mm Hg at peak exercise (p < 0.001). Five patients developed severe mitral regurgitation during exercise. CONCLUSIONS: Patients with exertional dyspnea and mild mitral stenosis and regurgitation at rest demonstrate a marked increase in pulmonary artery systolic pressure and mean transmitral pressure gradient during dynamic exercise. In a subset of these patients, marked worsening of mitral regurgitation appears to be the underlying mechanism of this hemodynamic deterioration. Because of the small sample size, this novel observation must be considered preliminary with respect to the true prevalence of exercise-related development of severe mitral regurgitation. If additional studies confirm the importance of this phenomenon, it has important implications for the management of patients with rheumatic mitral valve disease.
Adult↗
Treatment of malignant pericardial effusion.
OBJECTIVE: To discuss the diagnosis and treatment of malignant pericardial effusion and focus on quantitating the success and complication rates of the many treatment modalities and updating recent advances in the field. DATA SOURCES: English-language publications were identified by a computerized search (MEDLINE) of these key words: cancer, tumor, malignancy, pericardium, and pericardial effusion. This computerized search was supplemented by a manual search of the bibliographies of original research articles and textbooks. STUDY SELECTION: Studies were included if the outcome of patients undergoing treatment for malignant pericardial effusion was reported separately from the outcome of patients with other causes of pericardial effusions. Studies that only reported the combined results of patients with malignant and nonmalignant effusions were excluded. DATA EXTRACTION: To determine success rates for the various treatment modalities, we examined freedom from symptomatic recurrence of pericardial effusion requiring reintervention as the key end point. Where appropriate, we also examined procedural mortality rates. RESULTS: Initial relief of symptoms is achieved in most cases with percutaneous pericardiocentesis that, with echocardiographic guidance, can be performed with low morbidity and mortality. In many cases, drainage for several days with an indwelling catheter alleviates the effusion without subsequent recurrence. Systemic antitumor therapy with chemotherapy or radiation therapy is effective in controlling malignant effusions in cases of sensitive tumors such as lymphomas, leukemias, and breast cancer. Local sclerotherapy with tetracycline hydrochloride or bleomycin sulfate is also effective and associated with low morbidity. Sclerotherapy with other agents or radionuclides offers no advantages. Of the several surgical options, subxiphoid pericardiotomy has the advantage of low morbidity and mortality, can often be performed under local anesthesia, and is highly effective in preventing recurrence. Percutaneous balloon pericardiotomy has recently been described. This intervention is performed with local anesthesia, is effective in preventing reaccumulation, and has a low morbidity. CONCLUSIONS: Treatment of malignant pericardial effusions must be individualized with consideration given to the patient's condition and tumor type, the success rates and risks of the various modalities, and local availability and expertise.
Antineoplastic Agents↗
Preload does not influence nonmechanical O2 consumption in isolated rabbit heart.
Myocardial energy consumption for nonmechanical activity (excitation-contraction coupling) has been shown to be length dependent in isolated muscle studies but no more than minimally affected by preload in the whole heart. However, unloaded O2 consumption (VO2, which is used to estimate nonmechanical VO2 in whole heart) may not be accurate for quantifying nonmechanical energy consumption, because it contains VO2 for residual cross-bridge cycling. To more accurately determine the influence of left ventricular (LV) diastolic volume on nonmechanical VO2 in whole heart, we employed a new method for quantifying nonmechanical VO2, using the drug 2,3-butanedione monoxime (BDM). We measured VO2 and force-time integral during infusion of BDM (< or = 5 mM) at high (VH) and low LV volumes (VL) in 16 excised isovolumically contracting red blood cell-perfused rabbit ventricles. LV end-diastolic pressure was 9.7 +/- 4.6 and 3.8 +/- 2.8 (SD) mmHg at VH and VL, respectively. Nonmechanical VO2, estimated as the VO2-axis intercept of the linear VO2-force-time integral relation obtained during BDM infusion, did not differ significantly between VH and VL (0.0137 +/- 0.0083 and 0.0132 +/- 0.0090 ml O2.beat-1 x 100 gLV-1, P = 0.702). A multiple linear regression analysis for the pooled data confirmed this finding (P = 0.361). We conclude that, in the rabbit heart, LV diastolic volume does not importantly affect nonmechanical energy consumption over a physiological range of LV end-diastolic pressure. This indicates that length-dependent activation does not have an energetic cost in whole rabbit heart and suggests that its predominant mechanism is increased Ca2+ affinity for the contractile proteins.
Animals↗
Effects of free wall ischemia and bundle branch block on systolic ventricular interaction in dog hearts.
Systolic direct ventricular interaction is thought to occur via the ventricular septum and the coordinated contraction of common fibers shared by both ventricles. The purpose of the present study was to evaluate the effects of transient free wall ischemia and bundle branch block, which disrupt the coordinated contraction of shared common fibers, on left-to-right systolic ventricular interaction. We produced transient right and left ventricular free wall ischemia by 2-min coronary artery occlusions and bundle branch block by ventricular pacing in nine in situ dog hearts. To eliminate any confounding effect of series interaction, we used an abrupt hemodynamic perturbation (aortic constriction), and we measured systolic interaction gain (IG) as delta right ventricular peak systolic pressure/delta left ventricular peak systolic pressure (IG(peak)) and instantaneous delta right ventricular pressure/delta left ventricular pressure at matched data sampling times (IG(inst)), along with changes in right ventricular stroke volume and stroke work before and on the beat immediately after the aortic constriction. To achieve equivalence of the interventricular septal pressure transmission contribution to ventricular interaction, the delta left ventricular peak systolic pressure produced by the aortic constriction was matched under all experimental conditions [average increase: 64 +/- 19 (SD) mmHg]. Control IG(peak) was 0.12 +/- 0.05, and control IG(inst) was 0.11 +/- 0.05. These values did not change with either free wall ischemia or ventricular pacing, with or without an intact pericardium. The changes in right ventricular stroke volume and stroke work produced by the aortic constriction were not different from zero, during either ischemia or ventricular pacing, with or without an intact pericardium.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Mitral valve replacement versus mitral valve repair. A Doppler and quantitative stress echocardiographic study.
BACKGROUND: Standard mitral valve replacement (MVR) in patients with chronic mitral regurgitation results in consistent reductions in resting postoperative ejection fraction. This has been attributed to removal of the low-impedance ejection pathway into the left atrium or to disruption of the chordal apparatus. Mitral valve repair (MVP) does not reduce ejection fraction at rest. However, whether MVP confers any advantages with regard to dynamic left ventricular performance has not been investigated. The aim of this study was to directly compare standard MVR with MVP and to determine their respective influences on ventricular ejection performance during bicycle exercise. METHODS AND RESULTS: Ten consecutive patients with pure chronic mitral regurgitation who underwent MVP and 10 patients matched for age, sex, and preoperative ejection fraction who underwent standard MVR for pure chronic mitral regurgitation performed symptom-limited, graded upright bicycle exercise with simultaneous Doppler and quantitative two-dimensional echocardiography. Patients with MVP had significantly greater rest (55 +/- 12%) and exercise (63 +/- 11%) ejection fractions than matched patients with MVR (40 +/- 13% [P < .0001] and 42 +/- 17% [P < .005], respectively). End-systolic circumferential wall stress was significantly lower at rest (190 +/- 36 versus 244 +/- 46; P < .03) and at peak exercise (231 +/- 46 versus 300 +/- 52; P < .02) in patients with MVP. At peak exercise, left ventricular shape was significantly more spherical in patients with MVR than those with MVP (1.84 +/- 0.31 versus 2.45 +/- 0.59; P < .02). CONCLUSIONS: MVR with chordal transection resulted in significant reductions in rest and exercise ejection fraction. This was caused in part by a significant increase in end-systolic circumferential wall stress. MVP resulted in improved rest and exercise ejection indexes, primarily due to a marked reduction in end-systolic stress and maintenance of a more ellipsoidal chamber geometry.
Echocardiography, Doppler↗
Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction.
OBJECTIVES: The aim of this study was to identify dynamic predictors of exercise duration in patients with systolic left ventricular dysfunction and to test the hypothesis that left ventricular shape is an independent determinant of exercise duration in these patients. BACKGROUND: Measurements of left ventricular volumes and ejection fraction at rest do not predict exercise capacity in patients with systolic left ventricular dysfunction. Left ventricular shape at rest has been reported to be an independent determinant of exercise duration in these patients. The significance of alterations in left ventricular shape that occur during dynamic exercise has not been investigated. METHODS: Twenty-one patients with a documented ejection fraction < 40% performed symptom-limited graded upright bicycle exercise with simultaneous quantitative two-dimensional echocardiography. End-diastolic volume, end-systolic volume, stroke volume, ejection fraction and sphericity index were measured at rest and peak exercise. RESULTS: Eleven patients exercised beyond stage II (6 min, 50 W), averaging 8.9 +/- 1.9 min; 10 patients were unable to complete stage II, averaging 4.9 +/- 0.9 min. No patient developed clinical evidence of ischemia during the exercise period. Of the echocardiographic variables considered, only end-systolic and end-diastolic sphericity indexes at peak exercise (r = 0.809 and 0.711, respectively) and the change in end-systolic sphericity index during exercise (r = 0.697) were strongly correlated with exercise duration. CONCLUSIONS: Conventional descriptors of left ventricular function are poor predictors of exercise capacity. Dynamic changes in heart shape correlate strongly with exercise duration and may be important determinants of exercise capacity in patients with systolic left ventricular dysfunction.
Adult↗
Physiologic role of the normal pericardium.
Because of the characteristics of the parietal pericardial tissue, the intact pericardial sac has a limited reserve volume, becoming relatively non-compliant when the heart volume is at the high end of the normal physiologic range. Pericardial restraint of the heart is best considered as a contact force. Measured with flattened balloons, the magnitude of pericardial contact pressure is probably several mmHg less than right atrial pressure. The diastolic pressure-volume relationship of the right ventricle, and to a lesser degree of the left ventricle, shifts downward following pericardiectomy. In dogs, the pericardium has been shown to limit maximal cardiac output. Some disease states associated with a rapid increase in total heart volume, including subacute mitral regurgitation and right ventricular infarction, demonstrate an increased pericardial influence on cardiac filling.
Animals↗
Use of 2,3-butanedione monoxime to estimate nonmechanical VO2 in rabbit hearts.
The purpose of the present study was to evaluate the feasibility of partitioning myocardial O2 consumption (VO2) into mechanical and nonmechanical components in the whole heart preparation using a negative inotrope, 2,3-butanedione monoxime (BDM), which has been reported to have a selective effect on the contractile proteins in a low concentration range (< 6 mM). In six isolated bovine red blood cell-perfused rabbit hearts, VO2 and force-time integral (FTI) were measured during infusion of varying concentrations of BDM at a constant left ventricular volume chosen such that control left ventricular peak isovolumic pressure was approximately 100 mmHg. The VO2-FTI relation with BDM concentrations < or = 5 mM was highly linear (median r = 0.98). Its VO2-axis intercept at zero FTI had a positive value (mean 23% of control, 0.014 ml O2.beat-1 x 100 g-1). To confirm the selective effect of BDM on the contractile proteins, the intracellular free Ca2+ transient was measured with the fluorescent indicator indo 1 in three isolated buffer-perfused rabbit hearts. The amplitude of the Ca2+ transient was not altered by BDM at concentrations < or = 10 mM, although left ventricular developed pressure was markedly depressed. This finding indicates that BDM < or = 10 mM does not affect excitation-contraction coupling. We conclude that the VO2-axis intercept value of the VO2-FTI relation during BDM infusion in a low concentration range represents VO2 for nonmechanical energy utilization. The BDM method to partition VO2 into mechanical and nonmechanical components is thus feasible in the whole rabbit heart.
Animals↗
Increased left ventricular mass after thoracotomy and pericardiotomy. A role for relief of pericardial constraint?
BACKGROUND: Myocardial stretch and increased ventricular filling can lead to increased rates of myocardial protein synthesis. In animal studies, left ventricular mass increases after pericardiectomy, suggesting relief of a biologically meaningful restraining role and a resultant stimulus for growth. The present study was designed to test the hypothesis that combined thoracotomy and pericardiotomy leads to left ventricular hypertrophy in patients with normal left ventricular ejection fraction undergoing elective bypass surgery. METHODS AND RESULTS: Twenty-five patients with normal left ventricular ejection fraction without active myocardial ischemia underwent Doppler and quantitative two-dimensional echocardiography 1 day before and 6 weeks and 7 months after elective coronary artery bypass surgery. The pericardium was left widely incised in all patients. Left ventricular end-systolic volume, end-diastolic volume, stroke volume, ejection fraction, end-systolic circumferential wall stress, and mass were measured. Left ventricular end-diastolic volume index increased from 51 +/- 11 mL/m2 to 62 +/- 14 mL/m2 (p < 0.05) at 6 weeks and to 66 +/- 14 mL/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. Left ventricular mass index increased from 109 +/- 23 g/m2 to 127 +/- 24 g/m2 (p < 0.05) at 6 weeks and to 131 +/- 23 g/m2 (p < 0.05 versus baseline, p = NS versus 6 weeks) at 7 months. There were no changes in systolic or diastolic blood pressures, end-systolic circumferential wall stress, or end-systolic volume. CONCLUSIONS: Patients with normal left ventricular ejection fraction develop increases in left ventricular end-diastolic volume and mass after coronary artery bypass surgery. These findings support the hypothesis that the increase in left ventricular end-diastolic volume associated with thoracotomy and pericardiotomy leads to myocardial growth and an increase in left ventricular mass.
Coronary Artery Bypass↗
Exercise conditioning in older coronary patients. Submaximal lactate response and endurance capacity.
BACKGROUND: Older coronary patients are at high risk of cardiac disability. Exercise conditioning programs have been demonstrated to improve functional capacity, particularly in younger coronary patients. In this study, the effects of aerobic conditioning on submaximal and maximal indicators of exercise performance were examined in 45 older coronary patients. METHODS AND RESULTS: Forty-five patients (mean age, 69 +/- 6 years; range, 62 to 82 years) entered 3-month and 12-month (n = 11) endurance training programs. Training effects were assessed during an exhaustive submaximal exercise protocol with measurement of endurance time, serum lactate, perceived exertion, and expired ventilatory measures. Exhaustive endurance time increased by more than 40% (30 +/- 10 to 41 +/- 10 minutes), with associated decreases in serum lactate, perceived exertion, minute ventilation, heart rate, and systolic blood pressure during steady-state exercise. Respiratory exchange ratio during steady-state exercise, an indicator of substrate utilization, decreased, indicating a shift toward greater use of free fatty acids as a metabolic fuel. In a subset of 10 patients, percent body fat was decreased (32 +/- 8% to 29 +/- 10%) over a period of 3 months. CONCLUSIONS: Older coronary patients respond to aerobic conditioning with remarkable improvements in submaximal endurance capacity, out of proportion to the more modest increases in VO2max. Activities that were exhaustive before training became sustainable for extended periods of time at a lower perceived exertion. Measurements of serum lactate, respiratory exchange ratio, and ventilation during steady-state exercise document that at an identical absolute work load after conditioning, exercise is performed using aerobic substrate to a greater degree, and ventilatory response to a given work load is lessened.
Aged↗
Effects of amrinone and isoproterenol on mechanoenergetics of blood-perfused rabbit heart.
To compare the effects of amrinone (AMR) and isoproterenol (Iso) on left ventricular contractility and energetics, we assessed Emax (ventricular contractility index) and the relation between oxygen consumption per beat (VO2) and systolic pressure-volume area (PVA, a measure of left ventricular total mechanical energy) in isolated cross-circulated (blood-perfused) rabbit hearts during infusion of AMR or Iso in either a constant-flow (CF) or constant-pressure (CP) perfusion mode. Both Emax and the VO2 intercept of the linear VO2-PVA relation increased significantly during AMRCP (increase in Emax 15% and increase in VO2 intercept 11%), ISOCF (49 and 43%), and ISOCP (55 and 54%) but not during AMRCF. However, neither drug changed the slope of the VO2-PVA relation (reciprocal of contractile efficiency) in either perfusion mode. Furthermore, with both drugs the relation between increases in Emax and the VO2 intercept fell on a single regression line (r = 0.92). We conclude that 1) although the mechanism of action and inotropic potency of the two drugs differ, their effects on cardiac energetic cost are essentially the same, i.e., both drugs increase the nonmechanical oxygen cost in proportion to the increase in contractility without changing contractile efficiency, and 2) a significant portion of the inotropic effect of AMR in the whole ventricle is likely due to increased coronary blood flow, i.e., Gregg's phenomenon.
Amrinone↗
Absence of right ventricular isovolumic relaxation in open-chest anesthetized dogs.
During the left ventricular (LV) pump cycle, peak negative first derivative of pressure vs. time (dP/dt) occurs very close to the end of LV ejection, and there is a well-defined isovolumic relaxation period. Despite similarities between the right ventricular (RV) and LV pump cycles, recent studies indicate uncertainty as to whether peak negative RV dP/dt occurs simultaneously with RV end ejection and whether there is an isovolumic relaxation period during the RV pump cycle. To study these questions, we recorded relative timing of peak negative RV dP/dt, RV end ejection, and right atrial-RV pressure crossover in the open-chest anesthetized dog. The data demonstrate that peak negative RV dP/dt occurs an average of 60 ms before end ejection and that there is no RV isovolumic relaxation period. These findings have implications for the possible use of peak negative RV dP/dt as a marker of RV end ejection and for how time constants of pressure decay obtained during RV relaxation can be interpreted.
Anesthesia↗
2,3-Butanedione monoxime increases contractile efficiency in the rabbit ventricle.
The efficiency of chemomechanical energy transduction (contractile efficiency) of the left ventricle (LV) has been calculated from the linear correlation of the systolic pressure-volume area (PVA) of the LV and its O2 consumption (VO2). Thus far, a wide range of acute interventions, including adrenergic agents, Ca(2+)-sensitizing drugs, and Ca2+ channel blockers have not altered contractile efficiency. In contrast, hyperthyroidism has been reported to decrease contractile efficiency, an effect attributed at the cross-bridge level to an increase in the V1/V3 myosin isoenzyme ratio. We hypothesized that an acute intervention which directly alters cross-bridge cycling would also change contractile efficiency. Accordingly, 2,3-butanedione monoxime (BDM), a negative inotropic agent that is thought to directly inhibit cross-bridge formation, was administered to seven excised, red blood cell-perfused, isovolumically beating rabbit LVs. At 3-4 mM perfusate concentration, BDM resulted in the following reversible mechanical and energetic effects compared with control. Contractility, assessed by the slope (Emax) of the end-systolic pressure-volume relation, decreased by 11% (196.6 +/- 25.9 vs. 222 +/- 28 mmHg/ml). Both the time to end systole (Tmax) and relaxation half time (T1/2) decreased. The slope of the VO2-PVA relation decreased by 20% (1.55 +/- 0.44 x 10(-5) vs. 1.95 +/- 0.52 x 10(-5) ml O2 x mmHg-1 x ml-1), equivalent to an increase in contractile efficiency from 36.5 +/- 10.4 to 46.4 +/- 14.4%, while the O2 costs of the mechanically unloaded LV decreased by 12% (0.0258 +/- 0.0060 vs. 0.0292 +/- 0.0064 ml O2 x beat-1 x 100 g-1). Finally, BDM also produced coronary vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effect of coronary hyperemia on Emax and oxygen consumption in blood-perfused rabbit hearts. Energetic consequences of Gregg's phenomenon.
To assess the relation between increases in contractile function and oxygen consumption (VO2) during increased coronary flow (Gregg's phenomenon), we measured the end-systolic pressure-volume relation and the relation between VO2 and left ventricular systolic pressure-volume area (PVA, a measure of total mechanical energy output) in blood-perfused, isovolumically contracting rabbit hearts during control and intracoronary adenosine infusion. During adenosine infusion at a constant perfusion pressure (93 +/- 11 mm Hg), coronary flow increased by 99 +/- 76% (p less than 0.01), and the slope of the end-systolic pressure-volume relation, Emax (ventricular contractility index), increased by 18 +/- 15% (p less than 0.01). When compared at the same left ventricular volume, PVA increased by 20 +/- 14% (p less than 0.01) and VO2 by 19 +/- 15% (p less than 0.01) with adenosine. The VO2-PVA relation was linear under each condition (both median r = 0.98). With increased coronary flow, the VO2-intercept of the VO2-PVA relation (unloaded VO2) increased by 22 +/- 18% (p less than 0.01) without a change in the slope; that is, a parallel upward shift was observed, indicating that the contractile efficiency (energy conversion efficiency of the contractile machinery) remained constant. These increases in Emax and unloaded VO2 were not eliminated by beta-adrenergic blockade with propranolol. We conclude that increased coronary flow with adenosine at a constant perfusion pressure augments both Emax and the nonmechanical energetic cost for excitation-contraction coupling and basal metabolism via nonadrenergic mechanisms, without changing contractile efficiency.
Adenosine↗