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R Krams

Publications and source records attributed to R Krams.

At least 37 records · Page 2Linked to original sources
PubMed1997

Influence of data processing on cyclic variation of integrated backscatter and wall thickness in stunned porcine myocardium.

This study was performed to investigate the relationship between the cyclic variation of integrated backscatter and myocardial wall thickening in stunned myocardium. Different definitions of cyclic variation were evaluated to be able to compare with other studies. Ultrasound data were acquired from 10 open-chested Yorkshire pigs (25-33 kg) at baseline, during regional ischemia and during 30 min of stunning, using a broadband ultrasound transducer (3-7 MHz) sutured directly upon the left ventricular myocardial wall. Cyclic variation of integrated backscatter and myocardial wall thickening were calculated using three definitions obtained from the literature. Independent of the definition, cyclic variation of wall thickness and integrated backscatter were blunted during acute ischemia and returned transiently to or above baseline during the first minute of reperfusion, followed by a gradual decrease to a level under baseline during stunning. An early return of the cyclic variation of the integrated backscatter was not observed in pigs, independent of the data processing used. The relationship between integrated backscatter and wall thickness was maintained.

Animals↗
PubMed1997

Contribution of asynchrony and nonuniformity to mechanical interaction in normal and stunned myocardium.

In anesthetized pigs, we investigated whether asynchrony (delta T) and nonuniformity (regional differences) in contractility (delta E) could describe the interaction between normal and stunned myocardium. Mechanical interaction was evaluated by regional postsystolic work (PSW) before and after production of stunning by a 5-min occlusion of the left circumflex coronary artery [LCX (LCX stunning)] and a subsequent 10-min occlusion of the left anterior descending coronary artery [LAD (LAD stunning)]. delta T and delta E were intensified by intracoronary (LAD) infusions of dobutamine. From regional end-systolic pressure-segment length relationships, systolic segment shortening (SS), end-systolic elastance (E), external work (EW), and PSW were determined. LCX stunning decreased SSLCX from 14 +/- 2 (mean +/- SE, n = 9) to 10 +/- 2% and ELCX from 103 +/- 25 to 52 +/- 7 mmHg/mm, whereas the LAD region was unaffected. EWLCX decreased from 165 +/- 16 to 138 +/- 20 mmHg.mm, whereas PSWLCX increased from -4 +/- 6 to 8 +/- 3 mmHg.mm. Additional LAD stunning reduced SSLAD from 16 +/- 2 to 9 +/- 3% and ELAD from 79 +/- 10 to 31 +/- 6 mmHg/mm, without affecting SSLCX and ELCX. In the normal myocardium, PSWLAD increased and PSWLCX decreased, but, during local LAD dobutamine infusions after stunning, both PSWLCX and PSWLAD increased. In normal myocardium, the changes in PSWLCX could be described by delta T (65 +/- 11%) and delta E (37 +/- 15%). After stunning of the LAD area, the contribution of delta E increased to 55 +/- 14% at the expense of delta T (37 +/- 15%). Similar contributions of delta E (54 +/- 13%) and delta T (57 +/- 13%) were found when both the LCX and LAD distribution areas were stunned. In normal myocardium, both delta T and delta E modulate mechanical interaction, with the contribution of delta T exceeding that of delta E. In stunned myocardium, both factors contribute, but the contribution shifts in favor of delta E.

Animals↗
PubMed1997

Evaluation of endothelial shear stress and 3D geometry as factors determining the development of atherosclerosis and remodeling in human coronary arteries in vivo. Combining 3D reconstruction from angiography and IVUS (ANGUS) with computational fluid dynamics.

The predilection sites of atherosclerotic plaques implicate rheologic factors like shear stress underlying the genesis of atherosclerosis. Presently no technique is available that enables one to provide 3D shear stress data in human coronary arteries in vivo. In this study, we describe a novel technique that uses a recently developed 3D reconstruction technique to calculate shear stress on the endothelium with computational fluid dynamics. In addition, we calculated local wall thickness, the principal plane of curvature, and the location of plaque with reference to this plane, relating these results to shear stress in a human right coronary artery in vivo. Wall thickness and shear stress values for the entire vessel for three inflow-velocity values (10 cm/second, 20 cm/second, and 30 cm/second equivalents with the Reynolds numbers 114,229, and 457) were as follows: 0.65 +/- 0.37 mm (n = 1600) and 19.6 +/- 1.7 dyne/cm2; 46.1 +/- 8.1 dyne/cm2 and 80.1 +/- 16.8 dyne/cm2 (n = 1600). Curvature was 25 +/- 9 (m-1), resulting in Dean numbers 20 +/- 8; 46 +/- 16, and 93 +/- 33. Selection of data at the inner curvature of the right coronary artery provided wall thickness values of 0.90 +/- 0.41 mm (n = 100), and shear stress was 17 +/- 17, 38 +/- 44, and 77 +/- 54 dyne/cm2 (n = 100), whereas wall thickness values at the outer curve were 0.37 +/- 0.17 mm (n = 100) and shear stress values were 22 +/- 17, 60 +/- 44, and 107 +/- 79 dyne/cm2 (n = 100). These findings could be reconciled by an inverse relationship between wall thickness and shear stress for each velocity level under study. For the first time for human vessels in vivo, evidence is presented that low shear stress promotes atherosclerosis. As the method is nondestructive, it allows repeated measurements in the same patient and will provide new insights in the progress of atherosclerosis.

Coronary Angiography↗
PubMed1997

True reconstruction of vessel geometry from combined X-ray angiographic and intracoronary ultrasound data.

At present a rapidly expanding variety of methods appear to provide three-dimensional (3-D) reconstructions of blood vessels in a patient. Generally the results of such methods look very realistic. However, only a few produce a true 3-D reconstruction. We strongly suggest that for a true 3-D reconstruction of a blood vessel the following criteria should at least be fulfilled: (1) the arterial wall rather than the lumen must be reconstructed; (2) the spatially curved course of the vessel must be included; and (3) the orientation of local vessel wall characteristics, for example, plaque eccentricity, with respect to the luminal course must be correctly maintained. Currently, only methods combining biplane X-ray angiography and intravascular ultrasound imaging (IVUS) have succeeded in providing true 3-D reconstruction of a segment of a vessel. Accuracy of those reconstructions is derived from studies using phantoms having precisely known geometry. In patients, data on accuracy are more difficult to obtain. Nevertheless, a comparison can be made between the actual length of an IVUS pull-back trajectory and its reconstructed length showing relative differences of less than 3%. Further knowledge can be obtained by comparing simulated angiograms derived from the 3-D reconstruction with the real contrast angiograms. True 3-D reconstruction methods of the vessel wall and lumen, applicable in the individual patient, have become feasible and produce accurate results. Application of such a method will be helpful to understand immediate and long-term vessel remodelling induced by all types of catheter interventions and in the study of progression or regression of atherosclerotic wall disease.

Coronary Angiography↗
PubMed1996

The effect of a thiadiazinone derived Ca2+ sensitizer on the responsiveness of Mg(2+)-ATPase to Ca2+ in myofibrils isolated from stunned and nonstunned porcine and human myocardium.

Previously, we showed, in an in situ porcine model, that the thiadiazinone derivative [+]EMD 60263, a putative Ca2+ sensitizer with minimal phosphodiesterase III inhibitory properties, increased contractility more profoundly in stunned than in nonstunned myocardium. The aim of the present investigation was to study the mechanism of action by determining the in vitro effects of [+]EMD 60263 on the Ca2+ responsiveness of the Mg(2+)-dependent ATPases of myofibrils and sarcoplasmic reticulum membrane vesicles, isolated from normal ventricle of swine and hypertrophic septum of cardiomyopathic patients. Contamination of the myofibrils with sarcoplasmic reticulum membranes was excluded by testing the effect of the sarcoplasmic reticulum Ca(2+)-pumping ATPase inhibitor thapsigargin. The plasma concentrations at which [+]EMD 60263 exerted its inotropic effect in the in situ porcine model were found to be submicromolar. [+]EMD 60263 stimulated concentration-dependently (1-10 microM) the submaximally activated Mg(2+)-ATPases (at pCa 6.1) of pig heart myofibrils. [+]EMD 60263 (10 microM) shifted the pCa50 of porcine myofibrillar Ca(2+)-stimulated, Mg(2+)-dependent ATPase from 6.00 +/- 0.05 to 6.67 +/- 0.05, whereas the [-]enantiomer EMD 60264 had no significant effect. Although the effect was much less at 1 and 3 microM, [+]EMD 60263 (10 microM) also stimulated maximal myofibrillar Mg(2+)-ATPase activity. The Hill coefficient, reflecting the steepness of the fitted pCa/Mg(2+)-ATPase curve at half-maximal activation, was not affected by [+]EMD 60263 (10 microM). [+]EMD 60263 (10 microM) had no effect on sarcoplasmic reticulum Ca(2+)-stimulated, Mg(2+)-dependent ATPase from swine heart. The thiadiazinone derivative [+]EMD 57033 (10 microM), but not its [-]enantiomer EMD 57439, had similar, although less potent, effects on pig heart myofibrillar Mg(2+)-ATPase activity as compared to [+]EMD 60263. [+]EMD 60263 (3 microM) produced a significantly larger leftward shift of the pCa2+/Mg(2+)-ATPase activity curve of myofibrils isolated from the stunned compared to the adjacent nonstunned myocardium (Delta pCa50s caused by the presence of [+]EMD 60263 amounted to +0.57 +/- 0.04 and +0.42 +/- 0.05, respectively) in the in situ porcine model. The effects of [+]EMD 60263 on myofibrillar Mg(2+)-ATPase of hypertrophic human heart were identical to those observed with porcine heart myofibrils. The results indicate that the positive inotropic action of [+]EMD 60263 observed in the in situ porcine model of stunned myocardium may be primarily due to myofilament sensitization to Ca2+, and that this compound may have a similar action on diseased human myocardium.

Animals↗
PubMed1996

The relationship between myocardial integrated backscatter, perfusion pressure and wall thickness during isovolumic contraction: an isolated pig heart study.

To investigate the independent effect of myocardial wall thickness and myocardial perfusion pressure on integrated backscatter, experiments were designed in which integrated backscatter of normally perfused myocardial tissue was measured while changes in wall thickness during the cardiac cycle were reduced to a minimum. In nine blood-perfused isolated pig hearts, perfusion pressure was uncoupled from left ventricular pressure generation (Langendorff method) and isovolumic contraction and relaxation were realized by inserting a noncompressible water-filled balloon into the left ventricle. In a first experiment, at constant perfusion pressure (85 mmHg), the integrated backscatter (3-7 MHz), the myocardial wall thickness and the left ventricular pressure were determined simultaneously at various balloon volumes (5-25 mL). A quasistatic increase of balloon volume by 50% resulted in an average decrease of wall thickness of 6.5% (p < 0.01) and a mean increase in the integrated backscatter level of 1.1 dB (p < 0.01). Integrated backscatter levels increased statistically significant by 0.14 +/- 0.014 dB per percent decrease of wall thickness. Measurements of percentage end-systolic myocardial wall thickening ranged from -10% to +10%, mean 0.15 +/- 4.5% (NS from zero); whereas cyclic variation of integrated backscatter ranged from -3.9 to +3.9 dB, mean 0.19 +/- 1.5 dB (NS from zero). In a second experiment, at a constant midrange balloon volume, the same parameters were determined simultaneously at various perfusion pressures (20-120 mmHg). An increase in perfusion pressure by 50% resulted in a small but statistically significant increase of 1.5% in myocardial wall thickness, which could be explained by an increase of intravascular volume. The integrated backscatter levels did not change statistically significantly. Measurements of percentage end-systolic myocardial wall thickening ranged from -8.9 to +7.8%, mean 0.13 +/- 4.0% (NS from zero); whereas cyclic variation of integrated backscatter ranged from -1.8 to +4.2 dB, mean 0.37 +/- 1.3 dB (NS from zero). The magnitude of cyclic variation of integrated backscatter of myocardial tissue in a contractile state is reduced if myocardial muscle is prevented from normal thickening. In addition, changes in intravascular volume during the cardiac cycle have a negligible influence on the absolute backscatter level or its cyclic variation. We conclude, if only wall thickness and perfusion pressure are involved, that integrated backscatter is mainly determined by myocardial wall thickness.

Animals↗
PubMed1995

New invasive techniques of assessment of the physiological significance of coronary stenoses in humans.

Pressure and flow velocity can be measured distal to coronary stenoses by means of miniaturized sensors with guidewire technology. This is an alternative non-invasive method of assessing functional coronary vessel stenosis severity, applicable for the intermediate stenoses and for the results of coronary interventions. The complexity of the coronary circulation, however, limits the possibility of establishing simple cut-off criteria to identify flow-limiting stenoses. In this paper, we review advantages and limitations of the different pressure and velocity indices and their application in different clinical settings.

Blood Flow Velocity↗
PubMed1995

In vivo measurement of regional large artery compliance by intravascular ultrasound under pentobarbital anesthesia.

BACKGROUND: The presence of smooth muscle fibers on the wall of large arteries would suggest that arterial compliance might change in response to vasoactive substances. The purpose of this study is to determine the basal level of vasomotor tone in these arteries in a commonly used animal preparation and to learn whether the compliance of large conductance arteries can be altered in vivo by vasoactive agents. METHODS: Proximal iliac arterial compliance was measured in 7 pentobarbital-anesthetized pigs, before and during local infusions of adenosine and norepinephrine. Luminal area was measured every forty milliseconds by means of a 30 MHz intravascular ultrasound catheter and an automatic edge detection program. Simultaneous high-fidelity pressure measurements were obtained by means of a catheter-tipped pressure microtransducer positioned at the origin of the iliac artery. Linear regression analysis of the area/pressure relationship in two consecutive cardiac cycles (systolic phase only) was performed before and during adenosine and norepinephrine infusions. The slope of the area/pressure regression line was defined as an index of arterial compliance. Measurements after three minutes of infusions of adenosine (5-5000 micrograms/minute) and norepinephrine (0.001-10 micrograms/minute) were compared with the control measurements. RESULTS: Even at the highest infusion rate, adenosine did not significantly increase arterial compliance as compared with baseline (25 +/- 7 vs 19 +/- 4 mm2/mmHg x 10(-3), respectively, P = ns). In contrast, norepinephrine decreased arterial compliance as compared with the second baseline control (13 +/- 3 vs 20 +/- 3 mm2/mmHg x 10(-3), respectively, P < 0.01). CONCLUSIONS: In this animal model with pentobarbital anesthesia, arterial compliance may be modified more by the acute infusion of norepinephrine than by adenosine in large conductance arteries such as the proximal iliac. Thus, in this preparation, smooth muscle tone tends to be minimal and arterial compliance near maximal (ie, mostly a passive phenomenon). However, in response to norepinephrine, arterial compliance can decrease significantly as smooth muscle tone increases. Intravascular ultrasound allows continuous and accurate monitoring of these changes of arterial dimensions, suggesting that this technique may be useful in the evaluation of pharmacologically induced changes in the compliance of large arteries by vasoactive agents.

Adenosine↗
PubMed1995

Mechanical efficiency of stunned myocardium is modulated by increased afterload dependency.

OBJECTIVE: Oxygen consumption (MVO2) of stunned myocardium is relatively high compared to, and poorly correlated with, systolic contractile function. The aim of this study was to investigate whether an increased afterload dependency, induced by the decreased contractility of the stunned myocardium, contributes to the large variability in the mechanical efficiency data. METHODS: In 13 anaesthetised open thorax pigs undergoing two cycles of 10 min occlusion of left anterior descending coronary artery and 30 min reperfusion, segment shortening, the slope of end systolic pressure segment length relationship (Ees), external work (EW, derived from the area inside the left ventricular pressure segment length loop), the efficiency of energy conversion (EET, = EW/PLA x 100%, where PLA = total pressure-segment length area), mechanical efficiency (EW/MVO2), and their dependency on left ventricular end systolic pressure (Pes) were determined before and after induction of stunning, and during subsequent inotropic stimulation with dobutamine (1 and 3 micrograms.kg-1.min-1 over 15 min). RESULTS: The stunning protocol not only caused significant decreases in segment shortening, external work, energy conversion efficiency, and EW/MVO2 but also increased the afterload dependency of these variables. Before stunning an increase in Pes from 100 to 160 mm Hg decreased segment shortening from 18(SEM 1)% to 14(2)% (P > 0.05) and increased external work from 206(18) to 254(32) mm Hg.mm (P < 0.05). After induction of stunning the same increase in Pes caused a decrease in segment shortening from 9.5(1.8)% to -4.6(2.1)% (P < 0.05) and in external work from 149(21) to -11(10) mm Hg.mm (P < 0.05). The afterload dependency of the PLA was not altered by stunning, but the afterload dependency of energy conversion efficiency increased, since efficiency decreased from 67(3)% to 59(5)% as Pes was increased from 100 to 160 mm Hg before stunning, but from 57(5) to -7(5)% after induction of stunning (P < 0.05). Furthermore, the same increase in Pes resulted in an 8% decrease of EW/MVO2 before stunning and 107% after induction of stunning. Infusion of dobutamine not only restored segment shortening, external work, energy conversion efficiency, and EW/MVO2 of the stunned myocardium, but also attenuated their afterload dependency to pre-stunning levels. CONCLUSIONS: Myocardial stunning increases the afterload dependency of segment shortening, external work, energy conversion efficiency, and mechanical efficiency, which can be attenuated by inotropic stimulation with dobutamine. However, the decrease in left ventricular end systolic pressure, which accompanies the induction of stunning, counteracts the decrease in these variables. These two mechanisms can explain most of the reported scatter in mechanical efficiency.

Animals↗
PubMed1994

Loss of elastic recoil in postischemic myocardium induces rightward shift of the systolic pressure-volume relationship.

Ischemia-induced systolic dysfunction has been ascribed to changes in cellular excitation-contraction coupling and diastolic dysfunction because of disruption of the extracellular collagen matrix. Therefore, systolic and diastolic pressure-volume relationships and O2 consumption were determined before and after 5 min of global ischemia in isolated blood-perfused porcine hearts. The slope of the systolic pressure-volume relationship was 7.2 +/- 0.6 (SE) mmHg.ml-1.100 g-1 (n = 18) at baseline and did not change during reperfusion, but the systolic volume intercept shifted from 1.0 +/- 0.4 ml/100 g at baseline to 3.7 +/- 1.4, 4.1 +/- 1.1, and 4.2 +/- 0.9 ml/100 g at 15, 30, and 60 min of reperfusion, respectively (all P < 0.05). The diastolic volume intercept was 8.2 +/- 0.7 ml/100 g at baseline and remained unchanged during reperfusion. Therefore, the difference of the systolic-diastolic volume intercepts, an index of elastic recoil forces, was decreased to 57 +/- 8, 49 +/- 7, and 47 +/- 9% of baseline values (P < 0.05). The shift of the systolic pressure-volume relationship was accompanied by a transient decrease of contractile efficiency (slope of O2 consumption-pressure-volume-area relationship) at 15 min of reperfusion (from 43 +/- 6 to 27 +/- 7%). We hypothesize that the rightward shift of the systolic pressure-volume relationship was compatible with a decrease of elastic-restoring forces, probably induced by alterations in the extracellular collagen matrix and/or the cytoskeleton, and thereby our data imply that left ventricular dysfunction of postischemic myocardium does not result solely from disturbances in excitation-contraction coupling.

Animals↗
PubMed1994

Myofibrillar Ca2+ sensitization predominantly enhances function and mechanical efficiency of stunned myocardium.

BACKGROUND: Myocardial stunning is characterized not only by a decreased regional postischemic function but also by a relatively high oxygen consumption (ie, decreased mechanical efficiency). Several lines of evidence suggest that the underlying mechanism may involve a decreased sensitivity of the myofibrils to calcium, but in vivo evidence is lacking. We therefore evaluated this hypothesis in vivo using EMD 60263, a calcium-sensitizing agent, which is devoid of any phosphodiesterase-inhibiting properties. METHODS AND RESULTS: We first established the effect of two consecutive doses of EMD 60263 (0.75 and 1.5 mg/kg i.v., n = 7), administered at 15-minute intervals, on segment length shortening (SLS), external work index (EW; the area inside the left ventricular pressure-segment length loop), myocardial oxygen consumption (MVO2), and mechanical efficiency (EW/MVO2) in anesthetized pigs with normal myocardium. After the highest dose of EMD 60263, SLS in the distribution area of the left anterior descending coronary artery (LADCA) increased from 13 +/- 1% at baseline to 17 +/- 1% (P < .05). However, EW, MVO2, and EW/MVO2 were not significantly affected (123 +/- 10%, 98 +/- 9%, and 85 +/- 13% of baseline, respectively). In 14 other anesthetized pigs, myocardial stunning was induced by two sequences of 10 minutes of LADCA occlusion and 30 minutes of myocardial reperfusion. After induction of stunning, the two doses of EMD 60263 (n = 7) or saline (3 and 6 mL, n = 7) were infused. In the distribution area of the LADCA, the stunning protocol caused decreases in SLS from 16 +/- 1% to 8 +/- 1% (P < .05) and in EW to 49 +/- 5% of baseline (P < .05), whereas MVO2 was only minimally affected (P > .05). Consequently, mechanical efficiency decreased to 59 +/- 8% of baseline (P < .05). Saline infusion did not affect any of these regional myocardial variables, but after administration of EMD 60263 SLS recovered dose-dependently to 15 +/- 2% after the highest dose of the drug. EW and mechanical efficiency also recovered dose-dependently to 89 +/- 4% (P < .05 versus stunning) and to 88 +/- 7% (NS versus baseline) of baseline, respectively. In the not-stunned segment, SLS increased from 15 +/- 2% (at baseline) to 18 +/- 2% (after the highest dose), and EW per beat was not changed significantly. An adrenergic mode of action of EMD 60263 was excluded by blocking the alpha- and beta-adrenergic receptors with phentolamine and propranolol, respectively, 15 minutes before administration of EMD 60263 (ie, 15 minutes into the second reperfusion period) in five additional experiments. In these experiments the EMD 60263-induced increases in SLS and EW were not attenuated. Because EMD 60263 decreased heart rate from 106 +/- 4 to 76 +/- 3 beats per minute (P < .05) in the animals with stunned myocardium, we performed five experiments with the specific negative chronotropic compound zatebradine (UL-FS 49, 0.1 to 0.5 mg/kg) to rule out bradycardia as a factor contributing to the effects of EMD 60263. These zatebradine doses lowered heart rate from 116 +/- 5 to 55 +/- 1 beats per minute (P < .05) but had no effect on SLS of stunned and not-stunned myocardium. CONCLUSIONS: Calcium sensitization affects function and mechanical efficiency of stunned myocardium more profoundly than of not-stunned myocardium, lending support to the hypothesis that Ca2+ desensitization of the myofibrils is involved in myocardial stunning.

Animals↗
PubMed1994

Slope of the instantaneous hyperemic diastolic coronary flow velocity-pressure relation. A new index for assessment of the physiological significance of coronary stenosis in humans.

BACKGROUND: Coronary flow reserve (CFR), the functional index of stenosis severity more frequently used in the catheterization laboratory, is greatly affected by the hemodynamic conditions at the time of measurement and cannot be applied in the immediate assessment of the outcome of coronary interventions. The aim of the present study was to establish the feasibility and reproducibility of the assessment of the slope of the instantaneous diastolic relation between coronary flow velocity and aortic pressure during maximal hyperemia (IHDVPS) using a spectral analysis of the intracoronary Doppler signal, to assess the sensitivity and specificity of this index in the detection of flow-limiting coronary stenoses in comparison with CFR, and to study the possibility of determining the zero-flow pressure from the intercept of the velocity-pressure relation on the pressure axis during a controlled cardiac arrest. METHODS AND RESULTS: The instantaneous peak coronary flow velocity measured after intracoronary papaverine with a Doppler guidewire was plotted against the simultaneously measured aortic pressure, and the slope of the velocity-pressure relation in the phase of progressive diastolic velocity decrease was calculated during four consecutive beats. In nine normal arteries, a controlled diastolic cardiac arrest was induced by an intracoronary bolus injection of 3 mg adenosine. The IHDVPS could be assessed in 79 of 95 patients (83%), with a moderate intraobserver variability (0.4 +/- 11% after independent selection of different beats during maximal hyperemia). The IHDVPS showed no significant correlation with heart rate, mean diastolic aortic pressure, type of vessel studied, and cross-sectional area at the site of the velocity recording. The IHDVPS was significantly lower in arteries with > or = 30% diameter stenosis than in normal or near-normal arteries (0.71 +/- 0.48 versus 1.73 +/- 0.80 cm.s-1.mm Hg-1, P < .0000002). In the stenosis group, both IHDVPS and CFR were significantly correlated with the minimal luminal cross-sectional area (r = .46, P < .05 and r = .62, P < .002, respectively). The study of the velocity-pressure relation during long diastolic pauses showed a curvilinear relation between velocity and pressure in the lower pressure range, with an upward concavity to the velocity axis and no intercept with the pressure axis in most cases. CONCLUSIONS: The IHDVPS can distinguish between arteries with and without coronary stenoses and has a significant inverse correlation with the severity of the stenosis. Under the stable hemodynamic conditions of this study, the IHDVPS and CFR had similar sensitivities and specificities in distinguishing normal and stenotic vessels and demonstrated similar correlation with minimal luminal cross-sectional area. The curvilinearity of the velocity-pressure relation during long diastolic pauses, possibly due to a significant reduction of luminal cross-sectional area at low pressures, complicates the use of the flow velocity-pressure relation for the assessment of the zero-flow pressure.

Adult↗
PubMed1993

Intracoronary trimetazidine does not improve recovery of regional function in a porcine model of repeated ischemia.

We evaluated the effect of trimetazidine (TMZ) on recovery of regional cardiac function in anesthetized open-chest pigs, subjected to fifteen 2-minute occlusions of the left anterior descending coronary artery, separated by 2 minutes of reperfusion and a 120-minute recovery period. Regional myocardial function was evaluated by sonomicrometry-derived segment lengthening and the area enclosed by the left ventricular pressure-segment length loop (external work, EW) in animals, which received either an intracoronary infusion of TMZ (33 micrograms/kg/min, n = 6) or saline (1 ml/min, n = 7), starting 15 minutes before the first occlusion and ending 2 minutes after the 15th occlusion. In addition, myocardial malondialdehyde production to evaluate oxygen free radical production, oxygen consumption, and the ATP, ADP, and AMP content, as well as the energy charge, were determined at regular time intervals. In control pigs the sequences of occlusion-reperfusion did not affect systemic hemodynamics, except for the LVdP/dtmax, which decreased by 11% during the interventions and did not recover during the following reperfusion period of 2 hours (78% of baseline, p < 0.05). Systolic segment length shortening and EW were increased at the end of the first occlusion-reperfusion cycle, decreased gradually during the remainder of the occlusion-reperfusion periods, and did not improve during the recovery period. Energy charge and myocardial blood flow were not impaired, but oxygen consumption was decreased during the recovery period. The malondialdehyde data did not provide evidence for production of oxygen free radicals.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1993

Dobutamine restores the reduced efficiency of energy transfer from total mechanical work to external mechanical work in stunned porcine myocardium.

OBJECTIVE: In order to determine whether the relatively high oxygen consumption of stunned myocardium is related to decreased mechanical efficiency, myocardial oxygen consumption (MVO2) and its major determinants were studied in 10 open chest anaesthetised pigs. METHODS: According to the time varying elastance concept, MVO2 is determined by contractility (Emax) and total mechanical work (PLA), which is the sum of the external work (EW) and potential energy (PE). Mechanical efficiency (EW/MVO2) equals the product of EW/PLA (= efficiency of energy transfer or EET) and PLA/MVO2. Emax is the slope of the end systolic pressure-segment length relationship, determined by gradually clamping the aorta. PLA is the area enclosed by the end systolic pressure-segment length relationship and the pressure-segment length trajectory. EW is the area of the pressure-segment length loop. Systemic haemodynamics, regional segment shortening, and MVO2 were determined at baseline, during stunning (two sequences of 10 min occlusion and 30 min of reperfusion), after a subsequent 50 beats.min-1 increase in heart rate by atrial pacing and additional infusion of 2 micrograms.kg-1.min-1 dobutamine. RESULTS: Stunning decreased segment shortening from 18.2(SEM 1.9)% to 10.2(1.5)%, MVO2 from 4.16(0.27) x 10(-2) to 2.84(0.25) x 10(-2) mumol.beat-1.g-1, and Emax from 47(9) to 23(3) mm Hg.mm-1 (all p < 0.05). PLA decreased by 13(4)%, as EW decreased by 42(6)%, and PE tended to increase. Although EET decreased from 0.58(0.04) to 0.40(0.03) (p < 0.05), there was no decrease in the mechanical efficiency, as an increase in PE caused an increase in PLA/MVO2 which compensated for the decrease in EET. Dobutamine infusion increased Emax and EW per beat to 120(23)% and 67(8)% of baseline, respectively, while MVO2 [4.12(0.53) mumol.beat-1.g-1] and EET [0.57(0.04)] returned to baseline. CONCLUSIONS: In stunned myocardium, mechanical efficiency is not decreased despite a decrease in EET. The increase in EET after dobutamine may explain the lack of the excessive increase in MVO2.

Animals↗
PubMed1993

L-propionylcarnitine does not affect myocardial metabolic or functional response to chronotropic and inotropic stimulation after repetitive ischemia in anesthetized pigs.

In postischemic myocardium, fatty acid oxidation may be deficient owing to depletion of carnitine and citric acid cycle intermediates and fatty acylCoA-induced inhibition of adenine nucleotide translocase. During postischemic stress, the impairment of the fatty acid oxidation may become more apparent. We therefore investigated in open-chest anesthetized pigs the effect of L-propionylcarnitine [100 mg/kg per day orally (p.o.) for 3 days and 50 mg/kg intravenously (i.v.) 2 h before the first occlusion; n = 13] on myocardial function and metabolism of postischemic (two cycles of 10-min occlusion each followed by 30-min reperfusion) myocardium under resting conditions and during chronotropic and inotropic stimulation with dobutamine. Myocardial levels of free carnitine were higher after pretreatment (5.7 +/- 1.4 vs. 4.0 +/- 1.3 mumol/g protein, p < 0.05). The ischemia-reperfusion-induced decreases in free carnitine were similar for both the untreated and treated animals, but in the latter free carnitine was not different from the baseline levels in the control animals. In untreated animals (n = 15), regional systolic segment shortening (SS) was 18.5 +/- 5.5% (means +/- SD) at baseline, but was reduced to 5.1 +/- 5.5% (p < 0.05) at the end of the second reperfusion period. Myocardial ATP levels had decreased by 30% (p < 0.05) in the presence of a maintained energy charge, while myocardial oxygen and lactate consumption had decreased to 61% and 9% of baseline, respectively. During subsequent i.v. infusion of dobutamine (2 micrograms/kg/min), SS and myocardial oxygen consumption per beat increased to 75 and 65% of baseline, respectively, whereas lactate consumption per beat increased to only 25% of baseline. Decreases in myocardial ATP and oxygen and lactate consumption were not different between treated and untreated animals. L-Propionylcarnitine-treated animals displayed slightly better postischemic recovery of systolic SS than did control animals; to 39 and 28% (p = 0.056) of baseline, respectively, probably owing to a reduction in arterial blood pressure (BP), because L-propionylcarnitine prevented the increase in systemic vascular resistance produced by ischemia-reperfusion. L-Propionylcarnitine did not affect myocardial metabolic and contractile functional responses to chronotropic and inotropic stimulation. In a model of repetitive myocardial ischemia, L-propionylcarnitine prevents systemic vasoconstriction in response to ischemia and reperfusion and, probably as a result of the lower afterload, slightly ameliorates postischemic hypofunction, but loss of carnitine apparently does not play a role in myocardial hypofunction after brief repetitive ischemia and reperfusion in pigs.

Adenosine Diphosphate↗
PubMed1993

End-systolic pressure length relations of stunned right and left ventricles after inotropic stimulation.

Regional end-systolic pressure-segment length relationships (ESPSLR) were used to compare the degree of right and left ventricular stunning induced by a 10-min occlusion of the left anterior descending coronary artery and the response to subsequent atrial pacing (50 beats/min above intrinsic heart rate) without and with dobutamine (2 micrograms.kg-1.min-1) in nine anesthetized open-chest pigs. From the ESPSLR, the slope (Ees) (at 100 mmHg for the left and 25 mmHg for the right ventricle) and the total area of the pressure-length relationship (PLA) were determined. From the latter, the distribution into external work (EW) and potential energy (PE) as well as the efficiency of energy transfer (EET = EW/PLA) were calculated. In both the stunned left and right ventricular myocardium Ees and EW were reduced according to the same linear regression equations (delta Ees = 0.7 Ees,baseline - 11.4, r2 = 0.86 and delta EW = 0.4 EWbaseline + 2.3, r2 = 0.67), where Ees,baseline and EWbaseline are Ees and EW at baseline, respectively. EET of the stunned left and right ventricular segments decreased as PLA remained unchanged, due to an increase in PE. EET decreased from 0.84 +/- 0.02 to 0.71 +/- 0.03 (P < 0.05) in the stunned right ventricular segment and from 0.71 +/- 0.02 to 0.44 +/- 0.03 (P < 0.05) in the stunned left ventricular segment. Atrial pacing did not affect EET with respect to stunning levels, whereas the additional infusion of dobutamine restored Ees, EW, and PE and consequently EET to baseline values. In conclusion, the right ventricle is susceptible to stunning. During atrial pacing the EET was lower than expected from the Ees, which could, in agreement with the time-varying elastance concept, be explained by an increase in afterload (a consequence of the decrease in stroke volume). Dobutamine not only increased Ees, EW, and EET but also restored the relationship between Ees and EET in both ventricular stunned segments.

Animals↗
PubMed1993

Altered coronary flow reserve in the hypertrophied heart: implications for therapy.

Coronary flow reserve has been shown to be abnormally low in several models of left ventricular hypertrophy induced by long-standing pressure overload. Because the presence of hypertrophy is a risk factor for the development of subendocardial ischaemia and sudden death, efforts to restore alterations in flow reserve may prove beneficial. In the following review, we discuss potential mechanisms which might contribute to this abnormal vasodilator capacity in the hypertrophied heart, with particular emphasis on how chronic therapy may potentially reverse such abnormalities. In addition, we report how the acute administration of various classes of pharmacological agents can alter measurements of coronary flow reserve, as observed in our anaesthetised swine model. Such factors must be considered before interpreting any changes in coronary flow reserve in models of hypertrophy following chronic administration of drugs.

Animals↗