Time Constant Of Isovolumic Relaxation Research Articles

Isoflurane, but not halothane, improves indices of diastolic performance in dogs with rapid ventricular, pacing-induced cardiomyopathy.

The left ventricular (LV) mechanical effects of isoflurane and halothane were examined in dogs with rapid LV pacing-induced cardiomyopathy. These experiments tested the hypothesis that isoflurane and halothane differentially enhance indices of diastolic performance in dogs with moderate LV dysfunction. Eight dogs were chronically instrumented for measurement of LV and aortic pressures, subendocardial segment length, and cardiac output. Contractility was quantified by preload recruitable stroke work (Mw). Diastolic function was evaluated with a time constant of isovolumic relaxation (tau), segment lengthening velocities and time-velocity integrals during early filling (dL/dtE and TVI-E) and atrial systole (dL/dtA and TVI-A), and a regional chamber stiffness constant (Kp). Hemodynamics and LV function were recorded in the conscious state before pacing. The left ventricles of the dogs were then continuously paced at ventricular rates between 220 and 240 beats.min-1 for 10 +/- 1 days and monitored on a daily basis. After the development of moderate LV dysfunction, pacing was temporarily discontinued, and dogs were studied in sinus rhythm in the conscious state and after 20 min equilibration at 1.1, 1.4, and 1.7 minimum alveolar concentration isoflurane and halothane on separate days. Chronic rapid pacing increased baseline (sinus rhythm) heart rate, LV end-diastolic pressure, and end-diastolic segment length and decreased mean arterial pressure, LV systolic pressure, and cardiac output. Mw decreased and tau and Kp increased, consistent with LV systolic and diastolic dysfunction. Reductions in dL/dtE/dL/dtA and TVI-E/A occurred, which indicated that LV filling was more dependent on atrial systole. In dogs with cardiomyopathy, isoflurane and halothane increased heart rate and decreased mean arterial pressure, LV systolic pressure, LV end-diastolic pressure, cardiac output, Mw, and Kp. Decreases in LV end-diastolic pressure were more pronounced in dogs anesthetized with 1.1 minimum alveolar concentration isoflurane compared with halothane. Halothane-induced decreases Mw were greater than those observed with equi-minimum alveolar concentration isoflurane. A reduction in tau and increases in TVI-E/TVI-A and the ratio of early to total LV filling were observed with isoflurane. In contrast, halothane caused dose-related reductions in dL/dtE, dL/dtA, TVI-E, and TVI-A, and did not improve the ratios of these variables. Isoflurane, but not halothane, improved several indices of diastolic performance in dogs with pacing-induced LV dysfunction, despite producing simultaneous negative inotropic effects. These findings can probably be attributed to favorable reductions in LV preload and not to direct lusitropic effects. Improvement of filling dynamics may partially offset the decrement in LV systolic function by isoflurane in the setting of LV dysfunction.

Comparison of the cardiovascular effects of two novel superoxide dismutase mimetics, SC-55858 and SC-54417, in conscious dogs

The hemodynamic actions and left ventricular mechanical effects of two new superoxide dismutase mimetics, SC-55858 [Manganese (II) dichloro (2 R,3 R,8 R,9 R-bis-cyclohexano-1,4,7,10,13-pentaazacyclopentadecane)] ( n = 10) and SC-55417 [Manganese (II) dichloro (trans-2,3-cyclohexano-1,4,7,10,13-pentaazacyclopentadecane)] ( n = 8), were studied in chronically instrumented dogs in the conscious state and after 30 min equilibration at 0.033, 0.067, 0.233, and 0.667 μM · kg −1 · min −1 SC-55858 or SC-54417 (total doses of 1, 2, 7, and 20 μM · kg −1). SC-55858 and SC-54417 increased heart rate and decreased mean arterial pressure and left ventricular systolic and end-diastolic pressures. SC-55858 decreased preload recruitable stroke work slope and + dP dt max and increased the time constant of isovolumic relaxation, consistent with a direct negative inotropic and lusitropic effect. In contrast, SC-54417 did not depress left ventricular systolic and diastolic function. Decreases in mean arterial pressure caused by SC-55858 may be secondary to negative inotropic effects and reduction in cardiac preload. In contrast, SC-54417 does not depress myocardial contractility but also reduces arterial pressure via venodilation.

Effects and interactions of myocardial ischaemia and alterations in circulating blood volume on canine left ventricular diastolic function

We have determined the effects of alterations in preload on ischaemia-induced diastolic dysfunction in anaesthetized beagles instrumented to measure left ventricular pressure and regional dimensions. Low-flow regional ischaemia decreased peak lengthening rates in ischaemic (mean -26 (SEM 6) mm s-1, P < 0.01) and non-ischaemic (-8.6 (3.4) mm s-1, P < 0.05) myocardium. Peak lengthening rates and the time constant of iso-volumic relaxation (tau) were not affected by alterations in preload. Absolute values of tau failed to distinguish between ischaemia and control. The ischaemia-induced decrease in peak negative dP/dt was preload dependent and caused mainly by a concomitant decrease in peak left ventricular pressure. We conclude that indices derived from segmental lengthening are sensitive to ischaemia and insensitive to preload, in contrast with indices derived from left ventricular pressure. It remains to be determined if monitoring of early segmental lengthening will improve detection and assessment of perioperative myocardial ischaemia.

Unilateral changes of sympathetic tone to the heart impair left ventricular function

Different regions within the left ventricle are preferentially supplied by the left or right sympathetic system. In order to characterize different influences of left vs right sympathetic lateralization on LV function, haemodynamic effects of right and left stellate ganglion stimulations (RSGS and LSGS) as well as a right sympathetic block (RSB) were compared. Seven alpha-chloralose anaesthetized open chest dogs were instrumented for measurement of LV pressure (tip manometers) and regional LV wall thickness (WT, sonomicrometry) in the antero-apical wall (AW, innervated by right stellate ganglion) and postero-basal wall (PW, left stellate ganglion). Timing of regional myocadial wall motion was evaluated by the phase of the first Fourier transform of the WT signals, LV asynchrony by the phase difference (phi) between both regions, and LV diastolic function by the time constant of isovolumic relaxation (tau). Measurements were performed before and after RSB (5 ml of lidocaine 1%); in 6 dogs of this group, RSGS and LSGS (4 V, 0.2 ms, 20 Hz) were performed before RSB. In order to investigate a regional inotropic stimulation without systemic effect, 6 additional dogs received intracoronary noradrenaline injections (NIC, 0.25 microgram) into the left circumflex artery perfused myocardium. LSGS and NIC led to an earlier PW-motion within the cardiac cycle (phase reduction by 40.0 +/- 15.0 degree (SEM) and 55.5 +/- 11.2 degrees) and RSGS induced an earlier AW-motion (by 33.7 +/- 15.2 degrees). After RSB, AW-motion was delayed (38.1 +/- 9.2 degrees). The consequence was an asynchronous wall motion pattern after all interventions (change in phi: LSGS-64.7 +/- 18.7 degrees, RSGS 41.1 +/- 15.7 degrees, NIC -74.5 +/- 17.4 degrees, RSB -52.6 +/- 14.6 degrees), and a prolonged relaxation (tau increase: RSGS 9.4 +/- 1.9, NIC 8.3 +/- 1.5, RSB 3.7 +/- 0.8 ms). Unilateral increases as well as decreases of sympathetic tone to the heart result in an asynchronous wall motion pattern and an impaired LV relaxation.

Depression of cardiac function after deep hypothermic circulatory arrest in deeply anesthetized neonatal lambs

Cardiac dysfunction is common after neonatal cardiac operations. Previous in vivo studies in neonatal animal models however, have failed to demonstrate decreased left ventricular function after ischemia and reperfusion. Cardiac dysfunction may have been masked in these studies by increased endogenous catecholamine levels associated with the use of light halothane anesthesia. Currently, neonatal cardiac operations are often performed with deep opiate anesthesia, which suppresses catecholamine surges and may affect functional recovery. We therefore examined the recovery of left ventricular function after ischemia and reperfusion in neonatal lambs anesthetized with high-dose fentanyl citrate (450 μg/kg administered intravenously). Seven intact neonatal lambs with open-chest preparation were instrumented with left atrial and left ventricular pressure transducers, left ventricular dimension crystals, and a flow transducer. The lambs were cooled (<18º C) on cardiopulmonary bypass (22 ± 6 minutes), exposed to deep hypothermic circulatory arrest (46 ± 1 minutes), and rewarmed on cardiopulmonary bypass (30 ± 10 minutes). Catecholamine levels and indexes of left ventricular function were determined before (baseline) and 30, 60, 120, 180, and 240 minutes after termination of cardiopulmonary bypass. Levels of epinephrine, norepinephrine, and dopamine were unchanged from baseline values. Left ventricular contractility (slope of end-systolic pressure-volume relationship) was depressed from baseline value (31.7 ± 9.3 mm Hg/ml) at 30 minutes (15.7 ± 6.4 mm Hg/ml) and 240 minutes (22.7 ± 6.4 mm Hg/ml) but unchanged between 60 and 180 minutes. Left ventricular relaxation (time constant of isovolumic relaxation) was prolonged from baseline value (19.0 ± 3.0 msec) at 30 minutes (31.4 ± 10.0 msec) and 240 minutes (22.1 ± 2.8 msec) but unchanged between 60 and 180 minutes. Afterload (left ventricular end-systolic meridional wall stress) was decreased at 30, 60, and 240 minutes. Indexes of global cardiac function (cardiac output, stroke volume), preload (end-diastolic volume), and left ventricular compliance (elastic constant of end-diastolic pressure-volume relationship) were unchanged from baseline values. In deeply anesthetized neonatal lambs exposed to ischemia and reperfusion, left ventricular contractility, relaxation, and afterload are markedly but transiently depressed early after reperfusion and mildly depressed late after reperfusion. (J T HORAC C ARDIOVASC S URG 1996;111:359-66)

慢性心不全患者における強心薬ＯＰＣ‐１８７９０（Ｔｏｂｏｒｉｎｏｎｅ）の心血行動態および心筋エネルギー効率に及ぼす急性効果

We examined the acute effects and safety of OPC-18790 (toborinone), a novel water-soluble quinolinone derivative, on mechanoenergetics in 12 patients with chronic congestive heart failure. OPC-18790 was intravenously administered at a rate of 5μg/kg/ min or 10 μg/kg/min. Left ventricular (LV) pressure-volume data were obtained by conductance methods and myocardial oxygen consumption (MVO2) was measured using a Webster catheter.Heart rate was slightly increased in all patients after receiving OPC-18790. Ventricular preload as assessed by LV end-diastolic volume index significantly declined, and mean and systolic pulmonary artery pressure also fell after OPC-18790 infusion. In addition to venodilation, systemic vasodilation was observed after OPC-18790 infusion. Systolic and mean arterial pressure, and systemic vascular resistance significantly declined after OPC-18790 infusion. Effective arterial elastance (Ea), which represents both the mean vascular resistance and the pulsatile components, fell significantly.LV contractility as assessed by end-systolic elastance (Ees) significantly rose after OPC-18790 infusion. Cardiac index and ejection fraction improved significantly. External work (EW) was unchanged.The isovolumic relaxation time constant was prolonged before OPC-18790 infusion and OPC-18790 shortened this time constant rate. MVO2 was reduced after OPC-18790 infusion probably due to a reduction of wall tension. Ventricular-arterial coupling (Ea/Ees) was far less than optimal before OPC-18790 infusion and was near optimal after OPC-18790 infusion. Mechanical efficiency (EW/MVO2) was improved along with the Ea/Ees ratio. Systolic arterial pressure fell by 40 or 50 mmHg after OPC-18790 infusion in 2 patients probably due to vasodilation.In conclusion, OPC-18790 had favorable mechanoenergetic effects in patients with congestive heart failure. Despite enhancing contractility, OPC-18790 reduced MVO2 and improved mechanical efficiency probably due to its favorable effects on loading conditions. These findings suggest that OPC-18790 may be useful for short-term treatment of patients with congestive heart failure.

Dipyridamole slows the rate of isovolumic pressure fall in patients with normal coronary arteries.

Dipyridamole is currently used for thallium imaging and stress echocardiography. The coronary and haemodynamic effects of dipyridamole are well documented while its effects on left ventricular relaxation remain to be determined. The aim of the present study was to evaluate the effects of dipyridamole on left ventricular relaxation rate in healthy subjects. High fidelity pressure recordings were obtained at fixed atrial pacing (89 +/- 2 beats.min-1) in 10 subjects with normal left ventricular angiography and coronary arteriograms. Left ventricular pressure was recorded at rest and 5 min after a 4 min infusion of dipyridamole (0.14 mg.kg-1.min-1). Dipyridamole infusion decreased left ventricular systolic pressure (P < 0.01) and time to left ventricular systolic pressure (P < 0.01), with no changes in end-diastolic pressure or peak rate of pressure rise. The peak rate of isovolumic pressure fall decreased (from 1957 +/- 105 to 1488 +/- 100 mmHg.s-1, P < 0.01) and the time constant of isovolumic relaxation increased (from 37 +/- 2 to 44 +/- 3 ms, P < 0.02). In conclusion, our study indicates that acute administration of clinically relevant doses of dipyridamole displays deleterious effects on heart relaxation in healthy humans.

Load independence of radionuclide diastolic filling measurements in acute coronary occlusion

An accurate noninvasive method for measuring the effects of pharmacologic agents on active relaxation of the left ventricle would provide a valuable tool for monitoring the treatment of diastolic heart failure related to coronary artery disease. The time constant of isovolumic relaxation (T) and the left atrioventricular gradient were measured with micromanometer catheters and diastolic left ventricular filling variables were measured with radionuclide ventriculography in nine anesthetized, open-chest dogs with an acute coronary artery occlusion. Infusion of the positive inotropic drug dobutamine hydrochloride (5 to 10 micrograms/kg/min) resulted in a 35% shortening of T and a 37% increase in the radionuclide first-half filling fraction (both p < 0.05), but no change in the left atrioventricular gradient. Conversely, infusion of the alpha-adrenergic vasoconstrictor phenylephrine hydrochloride (20 to 40 micrograms/min) augmented left ventricular load, increasing the atrioventricular gradient by 45%, but had no significant effect on T or the first-half filling fraction. Infusion of the direct-acting vasodilator, sodium nitroprusside (80 to 120 micrograms/min), was accompanied by a 14% lengthening of T with a corresponding 28% decrease in the first-half filling fraction (both p < 0.05). In an anesthetized, open-chest canine model of acute myocardial ischemia, the radionuclide first-half filling fraction reflects pharmacologically induced changes in the lusitropic state of the left ventricle with relative independence of loading conditions.

Nature of heart failure in patients with ventricular septal defect

To assess the contributions of systolic and diastolic dysfunction to congestive heart failure (CHF) in ventricular septal defect (VSD), we studied 13 children with VSD at catheterization using a Millar catheter. Eight children had CHF, whereas five did not. Phenylephrine was infused at a rate of 5 micrograms.kg-1.min-1, and M-mode echocardiography and pressure were measured simultaneously. Systolic left ventricular (LV) function was assessed by maximum LV pressure (LVP), rate of pressure development (dP/dt), and by the end-systolic pressure-diameter relation (ESPDR). Systolic myocardial function was assessed by the end-systolic stress-strain relation. Diastolic chamber function was assessed by the isovolumic relaxation time constant (tau) and by the end-diastolic pressure-diameter relation (EDPDR). Diastolic myocardial function was measured by the end-diastolic stress-strain relationship. With phenylephrine, maximum LVP increased from 99 +/- 5 to 119 +/- 4 mmHg with CHF and from 106 +/- 6 to 149 +/- 10 mmHg without CHF. +dP/dt was lower with CHF (1,582 +/- 96 mmHg/s) than without CHF (2,300 +/- 200 mmHg/s). The maximum slope of the ESPDR was 39 +/- 8 with CHF and 94 +/- 14 mmHg/cm without CHF. The maximum slope of the midwall stress-strain relation was 223 +/- 37 with CHF and 395 +/- 93 g/cm2 without CHF. tau was 25 +/- 2 without CHF compared with 32 +/- 3 ms with CHF. The EDPDR was shifted leftward with failure, whereas the stress-strain relation was similar for all patients. CHF in patients with VSD results primarily from systolic dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of ryanodine on cardiac contraction, excitation-contraction coupling and “treppe” in the conscious dog

The effects of ryanodine on left ventricular (LV) function and hemodynamics were studied in 16 conscious dogs, chronically instrumented for measurements of LV pressures and dimensions. Systemic infusion of ryanodine (0.5-4 micrograms/kg i.v.) resulted in a dose-dependent depression of cardiac contraction. For example, ryanodine, 4 micrograms/kg i.v., decreased LV fractional shortening by 30.5 +/- 4.1%, LV dP/dt by 41.5 +/- 4.0% and Vcfc by 37.8 +/- 4.1%, while increasing the isovolumic relaxation time constant, tau, from 23.1 +/- 1.4 to 34.1 +/- 3.6 ms without a major effect on preload or afterload. Ryanodine also depressed (P < 0.05) the plateau phase of the mechanical restitution and post-extrasystolic potentiation responses, indicating a direct effect on excitation-contraction coupling. The heart rate dependent positive staircase ("Treppe") was significantly enhanced (P < 0.05) after ryanodine infusion, i.e. LV dP/dt rose by 43.1 +/- 4.7% with an increase in heart rate from 150 to 240 beats/min in the presence of ryanodine 4 micrograms/kg, but by only 7.5 +/- 2.1% without ryanodine. The more pronounced "Treppe" in the conscious dog under the condition of impaired SR calcium release caused by ryanodine, supports the concept that the classical Bowditch "Treppe" reflects either a state of myocardial depression due to alteration in SR calcium handling, or enhanced availability of trans-sarcolemmal Ca2+ influx. This finding may help to understand the discrepancy in the importance of the "Treppe" between conscious animals and more isolated preparations.

Systemic and coronary hemodynamic actions and left ventricular functional effects of levosimendan in conscious dogs.

We examined the effects of levosimendan, a new myofilament Ca2+ sensitizer with phosphodiesterase (PDE)-inhibiting properties, on systemic and coronary hemodynamics and left ventricular (LV) systolic and diastolic function in conscious dogs with intact and blocked autonomic nervous system (ANS) reflexes. Twenty experiments were conducted in 10 dogs chronically instrumented for measurement of aortic and LV pressure, the peak rate of increase and decrease in LV pressure (+dP/dtmax and -dP/dtmin), subendocardial segment length, diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). The slope (Mw) of the regional preload recruitable stroke work relation was used to assess myocardial contractility. Diastolic function was evaluated by -dP/dtmin, a time constant of isovolumic relaxation (tau), maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax), and a regional chamber stiffness constant (Kp). Dogs were randomly assigned to receive levosimendan (0.5, 1.0, 2.0, and 4.0 micrograms.kg-1.min-1) with or without ANS blockade. On separate experimental days, systemic and coronary hemodynamics and LV pressure-segment length diagrams and waveforms were recorded after 10-min equilibration at each dose in the conscious ANS-intact or ANS-blocked state. Levosimendan increased heart rate (HR), CO, mean and diastolic CBF velocity, and pressure-work index (PWI, an estimate of myocardial oxygen consumption) and decreased LV end-diastolic pressure (EDP), systemic vascular resistance (SVR), end-systolic and end-diastolic segment length, and mean and diastolic coronary vascular resistance (CVR) in dogs with intact ANS function. Levosimendan-induced increases in HR and PWI and decreases in SVR were attenuated by ANS blockade. Levosimendan caused equivalent dose-dependent increases in Mw in ANS-intact and ANS-blocked dogs, consistent with a positive inotropic effect independent of ANS activity. Levosimendan decreased tau (e.g., 35 +/- 1 ms during control to 29 +/- 1 ms at the high dose) and increased the magnitude of LV -dP/dtmin in dogs with intact but not blocked ANS reflexes, suggesting that relaxation was enhanced by favorable changes in systemic hemodynamics or ANS activation and direct effects of this drug on lusitropic state. Levosimendan also increased dL/dtmax to a greater degree in ANS-intact dogs, indicating that improvement of rapid ventricular filling was also partially dependent on ANS tone. No changes in Kp were observed in either experimental group. The results indicate that levosimendan decreases preload and afterload and has positive inotropic and lusitropic properties. The actions of levosimendan on diastolic function are largely mediated by the ANS.

Effect of negative intrathoracic pressure on left ventricular pressure dynamics and relaxation

To investigate the effect of a fall of intrathoracic pressure on left ventricular (LV) hemodynamics and relaxation, simultaneous micromanometric recordings of LV and aortic pressures were performed at rest and during two graded Mueller maneuvers in 16 patients undergoing cardiac catheterization for aortic valve stenosis (n = 8) or chest pain (n = 8). The reductions (means +/- SE) of airway pressure during the lesser and greater maneuvers were 26 +/- 1 and 42 +/- 1 mmHg, respectively. Simultaneously, LV isovolumic-developed pressure increased by 9 +/- 3 and 21 +/- 4 mmHg, respectively (P < 0.03 for both). During the greater maneuver, the individual changes of the time constant of LV isovolumic relaxation (tau) correlated with the changes of LV isovolumic-developed pressure (r = 0.73; P = 0.002). In patients with a > 20-mmHg rise in isovolumic-developed pressure, tau increased by 10.3 +/- 4.6 ms. By multiple-regression analysis, the change of tau was related directly to the change of isovolumic-developed pressure (standardized coefficient beta = 0.80; P = 0.001) and inversely related to the resting systolic LV-aortic pressure gradient (beta = -0.37; P = 0.050). The other hemodynamic changes were independent of aortic valve stenosis. In conclusion, during the Mueller maneuver, the LV isovolumic contraction load increases and tau lengthens, particularly with higher elevations of LV systolic load.

Mechanisms, diagnosis, and treatment of diastolic heart failure

Diastolic heart failure, in the absence of LV systolic dysfunction, is a common clinical condition that can be demonstrated in as many as one third of patients with congestive heart failure. Diastolic dysfunction caused by abnormalities in LV filling can be a result of many pathologic conditions, including hypertrophy, infiltrative cardiomyopathies, or myocardial ischemia. The major physiologic determinants of LV filling can be divided into cellular mechanisms, hemodynamic characteristics, and hormonal influences. Cellular mechanisms for impaired LV inactivation are determined by the handling of calcium within the myocyte during excitation—contraction—relaxation coupling. The hemodynamic characteristics of LV diastolic filling are determined by loading conditions, the time constant of isovolumic relaxation, heart rate, ventricular nonuniformity, pericardial restraint, myocardial elasticity, chamber compliance, and coronary blood flow. The sympathetic nervous system and the renin—angiotensin system are important modulators of diastolic filling, directly or indirectly. The diagnosis of heart failure is confirmed by a combination of clinical tests including invasive and noninvasive techniques, each of which has advantages and disadvantages. Treatment of medical conditions in which diastolic heart failure is a prominent component include pharmacotherapy with calcium channel antagonists, β-adrenergic blocking agents, diuretic agents, and angiotensin-converting—enzyme inhibitors. Certain conditions associated with diastolic filling abnormalities such as pericardial disease or severe ischemic heart disease may be best managed by surgical or percutaneous intervention. Future research will include further delineation of the cellular mechanisms of active myocardial relaxation and clinical investigation into treatment directed at improving outcome.

Direct Effects of Halothane and Isoflurane in Infant Rabbit Hearts with Right Ventricular Hypertrophy Secondary to Chronic Hypoxemia

In this study we compared the direct myocardial effects of halothane and isoflurane between chronically hypoxemic and normoxemic infant hearts with an isolated, perfused, nonworking rabbit heart model.Anesthetic effects were measured on heart rate, atrioventricular time, coronary flow, O2 consumption and extraction, and left and right ventricular peak systolic and end-diastolic pressures, + and -dP/dtmax; and tau, the time constant of isovolumic relaxation. Control values were similar between chronically hypoxemic and normoxemic groups except for variables affected by right ventricular (RV) hypertrophy in chronically hypoxemic hearts. For these variables values were significantly larger in the chronically hypoxemic group (P <or=to 0.05): coronary flow (12.3 +/- 0.4 vs 10.3 +/- 0.3 mL centered dot min-1 centered dot g-1), RV peak systolic pressure (68 +/- 3 vs 53 +/- 4 mm Hg), RV + dP/dtmax (1.42 +/- 0.07 vs 1.03 +/- 0.08 mm Hg/ms), and RV - dP/dtmax (-0.99 +/- 0.04 vs -0.78 +/- 0.08 mm Hg/ms). (Values are mean +/- SEM.) With anesthesia, values were similar between chronically hypoxemic and normoxemic groups except for coronary flow, which was significantly greater in chronically hypoxemic hearts for both anesthetics (14.1 +/- 0.9 vs 11.3 +/- 0.7 mL centered dot min-1 centered dot g-1 for halothane and 15.4 +/- 1.1 vs 12.2 +/- 0.6 mL centered dot min-1 centered dot g-1 for isoflurane). The degree of depression of RV peak systolic pressure and RV + dP/dt (max) by both anesthetics, and of RV -dP/dtmax by isoflurane, was significantly larger in chronically hypoxemic hearts because these hearts had greater control values but similar anesthetic values to normoxemic hearts. In this model, indices of myocardial function when the hearts were exposed to halothane and isoflurane were similar between chronically hypoxemic and normoxemic hearts except for coronary flow, which was greater in the chronically hypoxemic hearts. (Anesth Analg 1995;80:1122-8)

Disparate effects of early pressure overload hypertrophy on velocity-dependent and force-dependent indices of ventricular performance in the conscious baboon.

The effects of early pressure overload on left ventricular (LV) chamber mechanics in the primate heart are poorly understood. To test the hypothesis that early LV pressure overload hypertrophy is associated with depression of velocity-dependent indices of LV systolic (LV dP/dt) and diastolic function (time constant of relaxation, tau) but unchanged systolic elastance (Ees), we studied six conscious baboons instrumented with LV micromanometers and LV dimension and wall thickness sonomicrometers. Loading conditions were altered by pharmacological angiotensin II generation both before and 12 weeks after producing renovascular hypertension (2 kidney, 1 clip). The LV systolic pressure (149 +/- 11 [SD] versus 114 +/- 5 mm Hg) and LV mass (125 +/- 25 versus 91 +/- 20 g) were greater 12 weeks after than before (both P < .05). Both Ees and Ees normalized for LV mass were similar before versus 12 weeks after (23.0 +/- 9.6 versus 22.3 +/- 9.8 mm Hg/mL and 26.5 +/- 14.5 versus 19.8 +/- 12.5 mm Hg/mL, respectively; both P = NS). At matched LV systolic and diastolic pressures, LV fractional shortening was similar (18.6 +/- 6.8% versus 21.6 +/- 4.9%), but the time constant of LV isovolumic relaxation was significantly longer (42.3 +/- 5.3 versus 31.4 +/- 7.0 ms, P < .05) and LV dP/dt and Vcf were significantly less (1891 +/- 352 versus 2342 +/- 284 mm Hg/s and 0.9 +/- 0.4 versus 1.1 +/- 0.3 circ/s, respectively; both P < .05) 12 weeks after than before. In conscious baboons with systemic arterial hypertension and early LV hypertrophy, there is depression of velocity-dependent indices of LV contraction and relaxation but unaltered force-dependent measures of contractility.

1007-21 Effects of Changes in Atrioventricular Gradient and Isovolumic Relaxation Rates on Radionuclide Diastolic Filling in Man

The relative influences of the left atrioventricular gradient (AVG) and the time constant of isovolumic relaxation (TAU) on diastolic filling parameters by radionuclide angiography (RNA) in man are unknown. Therefore, 8 atrially paced patients without coronary artery disease underwent simultaneous RNA with micromanometer measurements of left atrial (LA) pressure, left ventricular (LV) pressure and TAU during baseline and steady-state infusions of nitroprusside (NIP), dobutamine (DOB), and phenylephrine (PHEN). RNA was acquired in 32 frames and Fourier fitted to obtain peak filling rate (PFR) and non-normalized PFR (NNPFR). Results below are % change (Δ%) from baseline ( ± SD). NIP (Δ%) DOB (Δ%) PHEN (Δ%) TAU 4 ± 11 –18 ± 7 * 11 ± 12 * LA pressure –25 ± 13 * –12 ± 11 * 52 ± 35 * AVG –27 ± 18 * –12 ± 29 82 ± 63 * PFR –8 ± 7 * –14 ± 12 * 6 ± 11 NNPFR –28 ± 9 * –21 ± 19 * 29 ± 29 * * p &lt; 005 Despite an augmented active relaxation with DOB, peak filling rate decreased significantly in response to decreased LA pressure. We conclude the RNA diastolic filling indices are critically dependent on the LA component of the AVG.

941-21 Exercise-induced Global and Regional Diastolic Dysfunction in Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is known to cause diastolic dysfunction. However, little studies have evaluated alterations in global and regional diastolic function during exercise in this disease. We studied 9 patients with HCM with asymmetric septal hypertrophy and normal systolic function with simultaneous recordings of micromanometer left ventricular (LV) pressure and M-mode echocardiogram. All patients had normal epicardial coronary arteries. The modulus of chamber stiffness was obtained by curve-fitting the diastolic pressure-volume (Teichholtz) data in exponential form. The modulus of regional myocardial stiffness was obtained by curve-fitting the relation between the mean wall stress and the natural logarithm of reciprocal of wall thickness of interventricular septum and the posterior wall in diastole in exponential form. Data were obtained at rest and during supine bicycle exercise (25 watts). LV end-diastolic pressure increased from 19 ± 6 to 33 ± 6 mmHg (p &lt; 0.01), but LV end-diastolic dimension was unchanged. LV minimum pressure increased from 10 ± 3 to 18 ± 6 mmHg (p &lt; 0.05), and the time constant of isovolumic relaxation (Raff and Glantz) increased from 72 ± 14 to 82 ± 7 msec (p &lt; 0.05). The left ventricular diastolic pressure-dimension (volume) relation shifted upward in all patients. The modulus of chamber stiffness increased from 0.7 ± 0.4 to 1.9 ± 1.3 (p &lt; 0.05). The modulus of regional myocardial stiffness at rest was greater in interventricular septum than that of the posterior wall (7.7 ± 4.2 vs. 5.2 ± 1.9, P &lt; 0.05). The regional myocardial stiffness constant increased significantly during exercise in interventricular septum (p &lt; 0.05), whereas it was not significantly changed in the posterior wall. In conclusion, both impaired relaxation and increased chamber stiffness are responsible for exercise-induced diastolic dysfunction in HCM, suggesting that exercise-induced ischemia of the hypertrophied myocardium may playa role.

Myocardial edema and compromised left ventricular function attributable to dirofilariasis and cardiopulmonary bypass in dogs

SUMMARY We investigated the relation between left ventricular dysfunction and myocardial edema in dogs with heartworm (Dirofilaria immitis) infection that were undergoing cardiopulmonary bypass. Dogs with and without D immitis were anesthetized by continuous thiopental infusion and were mechanically ventilated. Sonomicrometry crystals were placed on the long and short axes of the left ventricle, and a Millar pressure transducer was placed in the left ventricular chamber. Pressure-volume loops were digitized and continuously recorded. Dogs with and without D immitis were placed on standard hypothermic cardiopulmonary bypass, with 1 hour of aortic cross-clamp. Wet-to-dry weight ratio corrected for residual blood volume was used to quantitate the volume of myocardial edema. Preload recruitable stroke work was used as a preload-independent index of systolic function. Tau, the isovolumic relaxation time constant, was determined to assess diastolic relaxation. Dogs with D immitis had increased baseline myocardial wet-to-dry weight ratio. After cardiopulmonary bypass, myocardial edema increased in all dogs. Acute edema attributable to cardiopulmonary bypass decreased preload recruitable stroke work in all dogs of both groups, and dogs with D immitis could not be weaned from cardiopulmonary bypass. Myocardial edema increased diastolic relaxation times (τ) in dogs with and without D immitis. We conclude that cardiopulmonary bypass and heartworm infection induce myocardial edema. This edema compromises left ventricular systolic and diastolic function making D immitis an important confounding factor in weaning dogs from cardiopulmonary bypass.

Effect of tachycardia heart failure on the restitution of left ventricular function in closed-chest dogs.

Cardiac mechanical restitution and relaxation restitution are thought to be physiological correlates of the recovery kinetics of Ca2+ release mechanisms and sequestration capacity of the sarcoplasmic reticulum (SR). Since congestive heart failure is characterized by abnormal intracellular Ca2+ handling, we sought to delineate changes in mechanical and relaxation restitution produced by heart failure. Six dogs instrumented with left ventricular (LV) micromanometers and piezoelectric dimension crystals were studied under control conditions and after tachycardia heart failure (THF) produced by rapid LV pacing for 3 to 4 weeks. After priming at a basic cycle length of 375 ms, test pulses were delivered at graded extrasystolic intervals (ESIs). Mechanical response was assessed from single-beat elastance. Relaxation was assessed from the time constant of isovolumic relaxation (tau), the average rate of pressure fall during isovolumic relaxation (Ravg), and peak negative dP/dt, the first derivative of LV pressure. Normalized mechanical and relaxation responses plotted against ESI produced monoexponential curves of mechanical and relaxation restitution. THF depressed baseline contractile and relaxation parameters compared with control (end-systolic elastance, 4.7 +/- 0.4 versus 7.1 +/- 0.5 mm Hg/mL, P < .005; tau, 34.8 +/- 2.2 versus 26.7 +/- 1.2 ms, P < .05; all values mean +/- SEM). THF slowed mechanical restitution and delayed development of peak contractile response, with the time constant of mechanical restitution increasing from 61.8 +/- 6.9 to 100.2 +/- 9.6 ms, P < .01. THF abolished the biphasic behavior of relaxation restitution, and this relation was approximated by a single monoexponential function. There was no difference in the time constants of the first phase of relaxation restitution at control and after THF (TCR1, normalized 1/Ravg, 44.3 +/- 5.6 versus 42.0 +/- 8.5 ms, P = NS; TCR1, normalized (dP/dtmin)-1, 42.2 +/- 6.3 versus 36.7 +/- 4.3 ms, P = NS). These results indicate that THF alters the recovery kinetics of SR Ca2+ release to a significantly greater extent than those of SR Ca2+ sequestration and that the abnormal time course of Ca2+ availability to the myofilaments is the rate-limiting step in the recovery of cardiac function after a depolarization.

Left Stellate Ganglion Block Impairs Left Ventricular Function

Stellate ganglion block (SGB) is an established procedure for the diagnosis and treatment of chronic pain. SGB results in an acute sympathetic denervation of a part of the left ventricular (LV) wall innervated by the blocked ganglion, which may impair regional contractility. The resulting imbalance of myocardial contractility in different LV regions may affect LV function adversely by increasing LV asynchrony. Seven anesthetized open chest dogs were instrumented for measurement of aortic and LV pressure (tip manometers), cardiac output (CO, thermodilution), and regional LV wall thickness (WT, sonomicrometry) in the anteroapical (predominantly innervated by the right stellate ganglion) and posterobasal wall (left stellate ganglion). The contractility of both regions was assessed using the relationship between preload recruitable stroke work and end-diastolic WT relationship (MW). The timing of regional myocardial wall motion was evaluated by means of the phase of the first harmonic of the Fourier transform of the WT signals, LV asynchrony by the phase difference (PD) between both regions, and LV diastolic function by the time constant of isovolumic relaxation (tau). Measurements were performed before and after left SGB (LSGB). Mean arterial pressure was 105 +/- 25 (mean +/- SD) before and 97 +/- 10 mm Hg after LSGB (not significant). CO remained unchanged (3.09 +/- 1.03 vs 2.93 +/- 1.07 L/min). LSGB significantly reduced contractility in the posterobasal myocardium (MW -162 +/- 26 vs -80 +/- 7 mm Hg; P < 0.01), accompanied by a delay of regional wall motion within the cardiac cycle (phase 202 +/- 18 vs 223 +/- 17 degrees; P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)