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Biomedical subjects

B Crozatier

Publications and source records attributed to B Crozatier.

At least 55 records · Page 3Linked to original sources
PubMed1991

Increased negative inotropic effect of calcium-channel blockers in hypertrophied and failing rabbit heart.

The effects on ventricular function of calcium channel blockers and isoproterenol were studied in isovolumically beating perfused control rabbit hearts and in hearts subjected to a double pressure plus volume overload studied at the early phase of heart failure. In control hearts, isoproterenol produced an increase of systolic ventricular function and relaxation that was maximal at 10(-7) M. In failing hearts, inotropic state increase in response to isoproterenol was significantly smaller (P less than .01) with no observed lusitropic effect. In control hearts, verapamil and diltiazem produced dose-dependent decreases of ventricular function which were larger with verapamil than with diltiazem (median drug concentration50 of developed pressure was, respectively, 1163 +/- 131 nM and 4524 +/- 451 nM, P less than .001). In failing hearts, contractility decrease was larger than in control hearts (median drug concentration50 of developed pressure was 604 +/- 69 nM and 2691 +/- 580 nM with verapamil and diltiazem, respectively). In contrast, Ro 40-5967, a new calcium-channel blocker, did not produce reductions of inotropic state with concentrations up to 10(-5) M. All three calcium-channel blockers produced a 2-fold increase of coronary flow at 10(-6) M. We conclude that the deleterious effect of verapamil and diltiazem in heart failure is due, at least in part, to a direct depressant effect of these drugs on contractility, which is larger than in control hearts. Additionally, the in vivo sympathetic compensation is probably reduced, as indicated by the decreased ventricular responsiveness to isoproterenol.

Animals↗
PubMed1990

Left ventricular function and beta-adrenoceptors in rabbit failing heart.

Few models of heart failure (HF) are available for physiological and pharmacological studies. We report here a model of pressure plus volume overload induced in rabbits in which left ventricular (LV) function was studied in the conscious state after instrumentation of the animals with LV pressure catheter and ultrasonic crystals measuring LV diameter. Beta-Adrenoceptors were studied on crude membranes obtained from control (C) and HF rabbits using [3H]CGP 12177. LV weights and end-diastolic diameters were significantly increased in the HF group compared with the C group (by 79 and 38%, respectively). The percentage of diameter systolic shortening was decreased, in the control state, in rabbits with HF (15.3 +/- 1.6%) as compared with C rabbits (29.6 +/- 2.5%) and remained lower in the HF group when end-systolic pressures were matched. Chronotropic response to isoproterenol injection was significantly decreased in rabbits with HF compared with that of C rabbits. Beta-Adrenergic receptor density was decreased in rabbits with HF (39.3 +/- 3.7 fmol/mg) compared with C rabbits (56.7 +/- 4.2 fmol/mg) without affinity changes. This model of chronic HF thus produces a marked hypertrophy with ventricular dilatation and a depression of LV function within 2 mo, factors that are associated with a reduced cardiac responsiveness to catecholamines and a decreased ventricular beta-adrenergic receptor density.

Animals↗
PubMed1989

Left ventricular pressure-diameter relations in the conscious rabbit.

A model for the study of left ventricular (LV) contractility in a small species was developed using conscious rabbits previously instrumented with a LV catheter and ultrasonic crystals measuring LV internal diameter. Afterload increase produced by methoxamine infusion was associated with a reduction in heart rate from 272(SEM18) to 214(20) beats.min-1, p less than 0.01; and an increase in LV end systolic pressure from 76.3(4.1) to 101(6.5) mm Hg, p less than 0.001, and in end systolic diameter from 8.7(0.7) to 9.9(0.7) mm, p less than 0.01. For matched end systolic pressure and heart rate, the increase in inotropic state produced by noradrenaline infusion significantly shifted the pressure-diameter relation to the left. Similarly, end systolic pressure and diameter were significantly lowered by sodium nitroprusside infusion, with a reflex increase of heart rate; and a decrease in inotropic state produced by verapamil infusion was demonstrated by a significantly larger end systolic diameter for matched end systolic pressure and heart rate. The pressure-diameter relation was not modified by volume loading, which increased end diastolic diameter by 9.6(1.1)% with no evidence of a Bainbridge reflex. The mild depressant effect of diltiazem was not detected by peak dP/dt changes but was demonstrated by the analysis of end systolic pressure-diameter relations. The instrumented rabbit thus appears to be a sensitive model for studying LV function and the cardiovascular effects of drugs.

Animals↗
PubMed1989

Preload-induced curvilinearity of left ventricular end-systolic pressure-volume relations. Effects on derived indexes in closed-chest dogs.

End-systolic pressure-volume relations (ESPVRs) were analyzed in 10 closed-chest autonomically blocked dogs before and after volume loading that restored end-diastolic volume to its value measured in the control conscious state. Dogs had been previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals for measurements of major, anteroposterior, and septum-free wall diameters. Left ventricular volume was calculated with an ellipsoidal model in the left ventricular cavity. ESPVRs obtained during caval occlusion after volume loading were curvilinear as shown by the division of the relation into two parts. The initial part of the relation had a significantly smaller ESPVR slope (Ees, 12.0 +/- 1.8 mm Hg/ml) and ESPVR volume-axis intercept (Vd, - 3.5 +/- 0.8 ml) than the final part of the relation (19.5 +/- 3.1 mm Hg/ml and 0.0 +/- 0.6 ml, respectively, p less than 0.01). The end-diastolic volume-peak dP/dt relation showed a similar curvilinearity when end-diastolic volumes were larger than 1.5-1.7 times the minimal end-diastolic volume reached during caval occlusion. ESPVRs were not different during aortic constriction and caval occlusion when end-diastolic volume was small. In contrast, with large end-diastolic volumes, Ees and Vd were significantly smaller during caval occlusion than during aortic constriction. The final part of ESPVR (with small end-diastolic volume) had the same slope and intercept as that during aortic constriction. We conclude that preload produces a curvilinearity of ESPVR that significantly modifies derived indexes when the range of preload changes is large.

Animals↗
PubMed1988

Mechanical adaptation to chronic pressure overload.

According to Meerson, the adaptation to cardiac overload can be divided into three periods: the first stage, immediately after the initiation of the defect during which hypertrophy develops, followed by the stable hypertrophy phase (SHP), and a third phase of myocardial failure. Ventricular muscle contraction during SHP has been extensively studied both in vivo and in vitro with conflicting results. In isolated papillary muscles, most studies showed a normal or depressed contractility during chronic volume overload and a depressed inotropic state in pressure overload with a reduced maximal velocity of shortening which has been related to a myosin isozyme shift. In contrast, in conscious animals, haemodynamic status is usually described as preserved during SHP with a ventricular hyperfunction and a normal contractile function per unit of muscle. This was the basis of the concept of preload reserve and afterload mismatch described by Ross. However, mechanisms other than preload reserve may play a role during cardiac adaptation to pressure or volume overload. For instance, we recently showed in the early phase of pressure overload an increased inotropic state of the in situ heart with a change of the excitation contraction coupling evidenced by a modification of the force-frequency relations. Changes in the adrenergic receptors (density and/or affinity) may also contribute to the adaptation of the in situ heart to cardiac overload. They represent an important research area because they may explain, along with species and model differences, the discrepancies between in vivo and in vitro studies.

Adenosine Triphosphatases↗
PubMed1987

Regional ventricular segmental dynamics in normal conscious dogs.

Left ventricular (LV) subendocardial segmental behavior was analyzed during the whole cardiac cycle for different loading and inotropic conditions in six conscious dogs that were instrumented with ultrasonic crystals in the basal (B) and apical (A) LV regions, a LV micromanometer, and an aortic cuff occluder. There were large variations of A and B segmental behavior during isovolumic contraction and relaxation. In contrast, a linear relationship between A and B was observed during ejection but segmental shortening was larger during control in A than in B, whether it was expressed as a percentage of systolic shortening (34.6 +/- 1.1 and 25.0 +/- 1.2%, respectively; P less than 0.005), or whether segments were normalized for passive resting length. This linear relationship during ejection with a slope of 1.49 was not significantly modified by alterations of loading conditions or inotropic state. The larger A than B shortening, independent of the normalization procedure, is attributed to the regional stress distribution in the LV. The absence of regional and cycle invariance particularly during isovolumic phases prevents the inference of ventricular volume from a limited number of dimensions.

Animals↗
PubMed1987

Modification of force-interval relations during early adaptation to pressure overload in dogs.

Ventricular function was analyzed in the end-systolic and end-ejection pressure-volume diagrams in seven conscious dogs during acute aortic stenosis (AS) and sustained stenosis (SS) 24 h later. Dogs were previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular major and minor axes and parietal wall thickness. The end-ejection pressure-calculated volume points were significantly shifted to the left during SS as compared with those obtained during AS both during a regular atrial pacing (150 beats/min) and during spontaneous heart rate. Postpacing beats were not different during AS and SS. During AS, end-systolic volume was larger after short intervals (SI) between beats (22.5 +/- 1.6 ml) than after long intervals (LI; 20.8 +/- 1.7 ml) for a smaller end-systolic pressure (P less than 0.001). This difference was minimal during SS. When SS was compared with AS, the end-systolic and end-ejection pressure-volume points were significantly shifted to the left after SI but not after LI. This suggests an acceleration of the restitution process during SS that modifies ventricular force-frequency relations and increases ventricular function as compared with AS, particularly for high heart rates.

Adaptation, Physiological↗
PubMed1985

End-systolic left ventricular pressure-dimension shift during acute relief of volume overload in the conscious dog.

To test whether left ventricular (LV) end-systolic dimensions are determined only by end-systolic pressure for a given inotropic state, 7 conscious dogs were studied during abrupt closure of a fistula created between the left subclavian artery and the left atrial appendage. The dogs were instrumented with an LV pressure micromanometer and ultrasonic crystals measuring LV major- and minor-axis diameters and ventricular wall thickness. During beta-blockade treatment and for the same end-systolic pressure, closure of the fistula produced a 40% decrease in cardiac output; end-diastolic diameter decreased by 1.5 mm and end-systolic diameter decreased by 0.9 mm. Calculated end-systolic volume was similarly decreased by 1.3 ml for a decrease of 2.9 ml of end-diastolic volume. Thus, large end-diastolic dimensional variations associated with peripheral resistance decrease significantly modify the end-systolic pressure-diameter (and volume) relations in the conscious animal. It is suggested that indexes obtained from these relations should not be used in patients when systolic pressure variations are associated with large stroke volume variations.

Adrenergic beta-Antagonists↗
PubMed1984

Load sensitivity of ventricular force-interval relations in conscious dogs.

The influence of the interval between beats on myocardial contractility was examined in conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular major and minor diameters and parietal wall thickness during control state and after inflation of an aortic cuff. Ventricular contraction was measured during variations of diastolic intervals (DI) produced by respiratory arrhythmia or atrial pacing. During control before aortic stenosis, minor equator shortening (% delta L) increased slightly after long (L) DI compared with short (S) DI with a corresponding decrease of end-systolic stress. During aortic stenosis, LDI were associated with a significant increase of % delta L compared with SDI although end-systolic stress was larger. Thus end-systolic stress-diameter relations were not modified during control but they were significantly shifted to the left after LDI during aortic stenosis. Inotropic state is thus increased after LDI during acute pressure overload but not during control, suggesting that the restitution phenomenon is load sensitive.

Animals↗
PubMed1984

Left ventricular adaptation to sustained pressure overload in the conscious dog.

The early adaptation to aortic stenosis was studied in eight conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring left ventricular minor equator, left ventricular major axis, and ventricular wall thickness. Data were compared during control, acute inflation of a supravalvular aortic cuff occluder and 24 hours after aortic stenosis with and without beta-blockade. Acute aortic stenosis increased peak systolic pressure and end-systolic pressure with a decrease of percent systolic shortening of minor diameter (% delta L). Twenty-four hours after aortic constriction for heart rates, end-diastolic dimensions, and systolic pressures similar to those measured during acute aortic stenosis, % delta L was significantly increased, compared with acute aortic constriction, and was close to control values. End-systolic diameter was not significantly different from control during sustained pressure overload, although end-systolic stress was increased by 26.7 +/- 6.1% (P less than 0.01 with control), representing a leftward shift of the end-systolic stress-diameter relation. Similar results were obtained under beta-blockade. We conclude that there is, in this model of moderate pressure overload, a nonsympathetic increased inotropic state very early after aortic constriction.

Animals↗
PubMed1982

Role of myocardial restoring forces in the determination of early diastolic peak velocity of fibre lengthening in the conscious dog.

Factors determining peak velocity of fibre lengthening (dL/dtmax) were examined in 12 conscious dogs previously instrumented with a left ventricular pressure micromanometer and ultrasonic crystals measuring internal left ventricular diameter and myocardial segment length. dL/dtmax was studied during control state, atrial pacing, volume loading and methoxamine injection. The behaviour of dL/dtmax was similar in diameters and in segments. A significant correlation was found during control in each dog between dL/dtmax and the extent of systolic shortening (delta L). The effect of filling pressure on dL/dtmax appeared by comparing moderate volume loading and maximal volume loading where deltaL were similar while dL/dtmax was increased by 7.1% in segments and 20.2% in diameters. However, the effect of filling pressure on dL/dtmax was less pronounced that the effect of delta L since, for matched delta L during control and during volume loading, dL/dtmax increased by 37.9% while a 25% increase of delta L increased dL/dtmax by 55.6%. Heart rate and afterload changes did not appear as influencing dL/dtmax for matched deltaL. In conclusion, although and increased filling pressure does increased significantly dL/dtmax, the extent of systolic shortening, and thus restoring forces, appear as the primary determinant of peak velocity of fibre lengthening in basal conditions.

Animals↗
PubMed1982

Nonsympathetic increased inotropic state early after aortic insufficiency.

The very early left ventricular response to chronic volume overload induced by aortic insufficiency (AI) was examined in conscious dogs previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring internal diameter, segmental length, and parietal wall thickness. Acute volume loading with dextran (AVL) was compared with that 24 and 48 h after AI induced by a perforation of the aortic valve. beta-Blockade was also produced before and after AI. For a similar increase in preload in AVL and after AI, the percent change in systolic shortening of diameters and segments (% delta L) increased from 30.4 to 34.1% after AI (P less than 0.01). For matched calculated wall stress during AVL and AI, % delta L and peak velocity of shortening were significantly increased after AI, and the same results were reproduced after beta-blockade. We conclude that, at the early phase of chronic volume overload before hypertrophy appears, left ventricular hyperfunction is mainly due to a nonsympathetic increased contractility and that, in the conscious dog, the inotropic state appears to be modified by a sustained increased preload.

Adrenergic beta-Antagonists↗
PubMed1982

Relations between myocardial blood flow and postextrasystolic potentiation in epicardial and endocardial left ventricular regions early after coronary occlusion in dogs.

Postextrasystolic potentiation was studied during control and 5 minutes after coronary occlusion in epicardial regions of 12 open-chest dogs. Segmental behavior evaluated with ultrasonic crystals was correlated with regional myocardial blood flow (MBF) measured with radioactive microspheres. A similar correlation was found between the percentage of systolic shortening in postextrasystolic beats and MBF in epicardial (r = 0.64) and endocardial (r = 0.97) regions, although the scatter was much larger in the epicardium. The correlation was similar when segmental function was expressed as the area of the pressure-segment length loop. Three types of segments were described; completely ischemic segments (transmural MBF less than 5% of control), in which end-systolic length was larger than end-diastolic length after postextrasystolic potentiation; severely ischemic segments (5% less than or equal to transmural MBF less than 25% of control), in which the ischemic bulge during control beats was replaced by active shortening after premature ventricular complexes; and marginal segments (25% less than or equal to transmural MBF less than 100% of control), in which depressed shortening was enhanced close to control after a premature ventricular complex. These data reconcile conflicting studies, which did not consider similar degrees of ischemia and show a rapid loss of postextrasystolic potentiation in completely ischemic segments.

Animals↗
PubMed1981

Preload changes modify systolic pressure-diameter relations in the conscious dog.

The behavior of the end-systolic ventricular diameter was examined during control state, atrial pacing, and acute volume loading (VL) followed by methoxamine infusion in conscious dogs instrumented with a left ventricular micromanometer and ultrasonic crystals measuring internal diameter and wall thickness. Heart rate and systolic pressure were markedly increased by maximal VL but for moderate VL were minimally modified. Moderate VL increased end-diastolic diameter by 5% and end-systolic diameter by 2.9% with a significant increase of systolic stress. There was no common final pathway of shortening in the force-velocity-length diagram for different preloads. During methoxamine infusion, the end-systolic pressure-diameter points described a linear regression but points obtained during atrial pacing before VL were significantly shorter. We conclude that VL increases the total loading of the heart producing a lengthening of the end-systolic diameter when end-diastolic diameter is increased. This reduces the expression of the Starling mechanism and suggests caution when interpreting end-systolic pressure-diameter relations and derived indices for significantly different end-diastolic diameters.

Animals↗
PubMed1978

Myocardial infarction in the baboon: regional function and the collateral circulation.

Occlusion of the anterior descending coronary artery was produced in sedated baboons 7-15 days after implantation of a micromanometer and ultrasonic crystals for measurement of regional left ventricular dimensions in ischemic, marginal, and control segments. One minute after coronary occlusion (CO), ischemic segments exhibited a marked systolic bulge with wall thinning, and percent systolic shortening of marginal segments decreased. Over the ensuing weeks, there was a progressive increase of end-diastolic lengths in marginal and ischemic segments, whereas systolic shortening in these segments did not improve significantly. Control segments did not change. In control baboons, the coronary collateral index was 55 +/-25 (SE) compared to 560 +/- 74 in normal dogs. One month after CO, the collateral index was 543 +/- 144 in baboons compared to 6,685 +/- 716 in dogs, regions of normal tissue were seen in the infarct (14.2 +/- 2% of left ventricular mass). Minimal coronary collateral development in the baboon provides a likely explanation for differences from the dog in regional functional responses and in the character of the infarct.

Animals↗
PubMed1978

[Nitroglycerin in experimental myocardial infarction in the baboon. The effect of reducing the pre-charge and post-charge on regional myocardial function].

A left anterior descending coronary artery occlusion was produced in the sedated state in baboons previously instrumented with a left ventricular micromanometer and ultrasonic crystals measuring segmental myocardial lengths of control, marginal and ischemic regions. 3-8 days after the onset of the ischemia, nitroglycerin (0.4 mg IV) was injected. Following the injection (NG), heart rate increased significantly compared to the control ischemic state (CIS); end diastolic pressure and systolic pressure decreased significantly. In control segments, VCF increased from 0.99 +/- 0.11 circ/s to 1.26 +- 0.11 circ/s (p less than 0.01); in marginal segments VCF increased (CIS: 0.32 +/- 0.07 circ/s; NG: 0.42 +/- 0.09/s; p less than 0.01); in ischemic segments, the bulge observed before the injection persisted after nitroglycerin. Increased performances of control and marginal regions were attributed mainly to afterload reduction although preload reduction tended to decrease this response. The contribution of improved marginal function was small indicating that improvement of active hemodynamic function was largely due to changes in control segments function.

Animals↗