Pressure Work Index Research Articles

Acute response to cardiac re-synchronization therapy: ventricular properties adaptation?

Abstract Background Cardiac re-synchronization therapy (CRT) reduces mortality and hospitalization in patients with heart failure, reduced left ventricular ejection fraction (LVEF) and left bundle branch block (LBBB). However, there is no conclusive evidence on baseline parameters able to discriminate responder vs non-responder patients. Purpose In this study, we tested whether echocardiographic parameters describing LV dyssynchrony and efficiency may predict an acute LV recovery after CRT and whether lead position can modify such relationship. Methods We enrolled 65 consecutive patients (75% males, aged 71.2±10.5 years) referred for CRT according to current guidelines; 45% had an underlying ischaemic cardiopathy and 1/3 of them presented diabetes mellitus. We performed a CRT-off and CRT–on 2D and 3D echocardiography during devices optimization (time between programming change 10/12 min). We evaluated ventricular dyssynchrony by speckle-tracking analysis based on temporary uniformity of strain (TUS) 3D longitudinal and circumferential. We also derived non-invasive myocardial efficiency (Effic) by interaction between pressure work index (PWI), representing an estimation of myocardial oxygen consumption, and mechanical external work. We indicated as concordant those patients presenting a LV lead position (defined from a chest X-ray using 2 orthogonal views) in the same segment as the latest systolic 3D circumferential strain curves. Results In the CRT-on phase, a non-statistically significant raise in LVEF was observed [from 0.37 (0.28–0.46) to 0.41 (0.34–0.47), p=0.27]. No improvement in both longitudinal and circumferential 3D TUS was demonstrated during CRT-on (p=0.44 and 0.47, respectively). Conversely, the gain in Effic from CRT-off to CRT-on phase was overall significant (from 0.43±0.14 to 0.50±0.16; p<0.001). After switching to CRT-on, the increase in longitudinal 3D TUS was higher in concordant compared to discordant patients (from 0.83±0.08 to 0.87±0.07 vs 0.88±0.11 to 0.87±0.12, respectively), but without significant interaction (interaction p 0.24). No interaction was also found between variations of PWI after switching to CRT-on and LV lead position (concordant: from 12.99±4.18 to 12.84±2.99 ml/min/100g; discordant: from 13.58±3.89 to 13.95±3.97 ml/min/100g; interaction p 0.75). Conclusions Effic was overall acutely augmented during CRT-on phase in patients with LV dysfunction undergoing cardiac re-synchronization. In the acute phase, no significant relationship between LV changes in speckle-tracking analyses after CRT and LV lead position was found. 2-way ANOVA for myocardial efficiency Funding Acknowledgement Type of funding source: None

Microvascular response to metabolic and pressure challenge in the human coronary circulation

In vivo observations of microcirculatory behavior during autoregulation and adaptation to varying myocardial oxygen demand are scarce in the human coronary system. This study assessed microvascular reactions to controlled metabolic and pressure provocation [bicycle exercise and external counterpulsation (ECP)]. In 20 healthy subjects, quantitative myocardial contrast echocardiography and arterial applanation tonometry were performed during increasing ECP levels, as well as before and during bicycle exercise. Myocardial blood flow (MBF; ml·min(-1)·g(-1)), the relative blood volume (rBV; ml/ml), the coronary vascular resistance index (CVRI; dyn·s·cm(-5)/g), the pressure-work index (PWI), and the pressure-rate product (mmHg/min) were assessed. MBF remained unchanged during ECP (1.08 ± 0.44 at baseline to 0.92 ± 0.38 at high-level ECP). Bicycle exercise led to an increase in MBF from 1.03 ± 0.39 to 3.42 ± 1.11 (P < 0.001). The rBV remained unchanged during ECP, whereas it increased under exercise from 0.13 ± 0.033 to 0.22 ± 0.07 (P < 0.001). The CVRI showed a marked increase under ECP from 7.40 ± 3.38 to 11.05 ± 5.43 and significantly dropped under exercise from 7.40 ± 2.78 to 2.21 ± 0.87 (both P < 0.001). There was a significant correlation between PWI and MBF in the pooled exercise data (slope: +0.162). During ECP, the relationship remained similar (slope: +0.153). Whereas physical exercise decreases coronary vascular resistance and induces considerable functional capillary recruitment, diastolic pressure transients up to 140 mmHg trigger arteriolar vasoconstriction, keeping MBF and functional capillary density constant. Demand-supply matching was maintained over the entire ECP pressure range.

Heterogeneity and prediction of hemodynamic responses to dobutamine in patients with septic shock

To establish the heterogeneity of hemodynamic responses to dobutamine in patients with septic shock and to identify the predictive factors of these hemodynamic responses. Prospective study. A total of 12 patients with septic shock in a tertiary medical intensive care unit. A 20-min dobutamine infusion at 5 microg.kg(-1).min(-1) with subsequent increments to 8, 12.6, and 20 microg.kg(-1).min(-1), on two consecutive days. Responses were dichotomized into changes in heart rate (HR) or stroke volume index (SVI) of >10% and < or =10% at the maximal dobutamine infusion. No differences were found in survival, Acute Physiology and Chronic Health Evaluation II score, maximal dobutamine doses, or pharmacokinetics of dobutamine between HR and SVI groups. In DeltaHR > 10% vs. DeltaHR < or = 10%, baseline HR was lower, and baseline mixed venous oxygen tension and saturation were higher. During dobutamine infusion, mean arterial pressure decreased in DeltaHR > 10%. Cardiac index and the systemic oxygen delivery index increased and the systemic vascular resistance index decreased at unchanged SVI. Pressure work index increased and the ratio of the diastolic to systolic aortic pressure time indices decreased but not to <0.6. In DeltaHR < or = 10%, systemic vascular resistance index and the ratio of the diastolic to systolic aortic pressure time indices decreased (but remained >0.6) without changes in SVI or cardiac index. Baseline hemodynamic and metabolic variables did not differ between SVI groups. In DeltaSVI > 10%, cardiac index increased with dobutamine, but Pao2 and the systemic oxygen delivery index decreased. In DeltaSVI < or = 10%, HR and the systemic oxygen delivery index increased; mean arterial pressure, left ventricular stroke work index, systemic vascular resistance index, and the ratio of the diastolic to systolic aortic pressure time indices decreased. Patients with a positive chronotropic response to dobutamine had lower baseline HR values, and a chronotropic rather than inotropic response predicted an increase in cardiac index and systemic oxygen delivery index. Incremental dosages of dobutamine did not compromise indirectly measured myocardial oxygen balance.

Comparison of the effects of dexmedetomidine and esmolol on myocardial oxygen consumption in dogs

The beta-adrenergic blocker esmolol and the alpha 2-adrenergic agonist dexmedetomidine have the potential to decrease perioperative myocardial ischaemia. The pathophysiological mechanisms involved in these anti-ischaemic properties have not been thoroughly studied. We compared the effects of esmolol and dexmedetomidine on two indices of overall myocardial oxygen demand and on directly measured myocardial oxygen consumption of the left anterior coronary artery territory. Eleven mongrel dogs were instrumented to measure aortic and left ventricular pressure, aortic and left anterior coronary artery flow and myocardial wall thickening. Variables related to myocardial oxygen metabolism were also determined. Measurements were performed during four sequential experimental conditions in each dog (Control 1: esmolol; Control 2: dexmedetomidine). Esmolol and dexmedetomidine decreased haemodynamic indices of myocardial oxygen demand to a similar extent: esmolol decreased the rate-pressure product by 16+/-3% and the pressure-work index (PWI) by 16+/-3%, dexmedetomidine decreased the rate-pressure product by 26+/-3% and the PWI by 16+/-7%. However, these similar decreases resulted from different haemodynamic effects of the two study drugs. Dexmedetomidine had a more pronounced bradycardic effect than esmolol (P = 0.01) and increased systolic aortic pressure (SAP) by 15+/-4% while esmolol decreased SAP by 8+/-2% (P < 0.01). dP/dt(max) and regional myocardial area decrease were lower after esmolol than after dexmedetomidine. Neither drug had an effect on myocardial oxygen consumption. Esmolol and dexmedetomidine decreased two haemodynamic indices of overall myocardial oxygen demand to a similar extent but neither drug decreased directly measured myocardial oxygen consumption in the territory of the left anterior descending artery.

The interaction of MCI-154, a calcium sensitizer, and isoflurane on systemic and coronary hemodynamics in chronically instrumented dogs.

We conducted this study to determine the interaction of MCI-154, 6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a calcium sensitizer, and isoflurane on myocardial contractility as well as systemic and coronary hemodynamics in chronically instrumented dogs after pharmacological autonomic nervous system activity blockade. MCI-154 increased heart rate and left ventricular function with no change in rate pressure product, pressure work index, and coronary blood flow, with a decrease in coronary vascular resistance (CVR) in the conscious state. Isoflurane decreased heart rate and left ventricular function, with a decrease in rate pressure product and pressure work index. Isoflurane also decreased CVR, but not coronary blood flow. The cardiovascular actions of MCI-154 during isoflurane anesthesia were qualitatively similar to those observed in the conscious state. In contrast to the finding in the conscious state, MCI-154 reversed the decrease in cardiac output and preload recruitable stroke work caused by isoflurane, but these are not significantly different from the effects of isoflurane alone. These results indicate that MCI-154 increases myocardial contractility and decreases CVR without changing calculated myocardial oxygen consumption during both the conscious state and isoflurane anesthesia. MCI-154, a calcium sensitizer, restores the myocardial contractility depressed by isoflurane and enhances the coronary vasodilating effect of isoflurane in chronically instrumented dogs.

How silent is perioperative myocardial ischemia? a hemodynamic, electrocardiographic, and biochemical study in patients undergoing coronary artery bypass graft surgery

Objective: To analyze the relationship among Holter electrocardiogram (ECG) recordings, hemodynamic measurements indicative of global myocardial oxygen balance, and serum cardiac troponin I concentrations (cTnl) in the early postoperative period after coronary artery bypass graft (CABG) surgery. Design: Prospective observational study. Setting: University teaching hospital. Participants: Thirty patients undergoing CABG surgery. Interventions: ECG measurements consisted of Holter and standard ECG recordings. Hemodynamic measurements included heart rate, systolic and diastolic blood pressure (SBP, DBP), pulmonary capillary wedge pressure, and cardiac index (CI). Derived indices included tension time index (TTI), rate-pressure product, pressure work index (PWI), and endocardial viability ratio (EVR). Serial measurements of cTnl concentrations were measured postoperatively; the area under the cTnl concentration time curve was calculated for each patient (AUC cTnl). Measurements and Main Results: Episodes of myocardial ischemia were associated with small but significant rises in SBP ( p = 0.01), DBP ( p = 0.001), and TTI ( p = 0.005) compared with periods without ischemia in the same patients. Serum cTnl concentrations 24 hours after cardiopulmonary bypass ( p = 0.03) and AUCcTnl ( p = 0.01) values were greater in patients who developed ECG myocardial ischemia compared with patients who did not. Conclusions: The small changes in hemodynamics seen, although statistically significant, are unlikely to be the primary cause of the ischemia. They more likely reflect an independent process that causes or occurs as a result of ischemic episodes. Ischemic episodes detected by the Holter monitor are associated with significant release of cardiac troponin from the myocardium.

Propofol, but not thiopentone or etomidate, enhances isoflurane-induced coronary vasodilatation in dogs.

To test the hypothesis that thiopentone, propofol, and etomidate alter the coronary vascular effects of abruptly administered isoflurane. Dogs (n = 6) received inspired isoflurane 5% in the presence of thiopentone (20 mg.kg-1 induction dose and 20 mg.kg-1.hr-1 infusion), propofol (5 mg.kg-1 induction dose and 40 mg.kg-1.hr-1 infusion), etomidate (2 mg.kg-1 induction dose and 5 mg.kg-1.hr-1 infusion), or isoflurane (1.0 MAC) anaesthesia in a random fashion. Haemodynamics were assessed in the conscious state, during baseline anaesthesia, and at 30 sec intervals for five minutes after beginning isoflurane 5%. Rapidly administered isoflurane caused greater (P < 0.05) reductions in coronary vascular resistance in thiopentone- or propofol--than in isoflurane-anaesthetized dogs. Isoflurane produced greater (P < 0.05) increases in the ratio of coronary blood flow velocity to pressure-work index (an index of myocardial oxygen consumption; +109 +/- 19% during isoflurane alone vs +182 +/- 27% change from baseline during propofol and isoflurane) consistent with relatively greater direct coronary vasodilatation during baseline propofol than during baseline isoflurane anaesthesia. Isoflurane caused larger increases in coronary blood flow velocity in dogs anaesthetized with etomidate concomitant with higher coronary perfusion pressure and pressure-work index than in those anaesthetized with isoflurane alone. The results suggest that thiopentone, propofol, and etomidate each uniquely modify the coronary vascular responses to abrupt administration of high inspired concentrations of isoflurane in chronically instrumented dogs.

Increases in inotropic state without change in heart rate: Combined use of dobutamine and zatebradine in conscious dogs

The cardiovascular and left ventricular functional effects of dobutamine (5, 10 and 20 μg kg −1 min −1) were examined in conscious, chronically instrumented dogs in the presence and absence of control of heart rate with the specific bradycardic agent, zatebradine. Dobutamine increased heart rate, cardiac output, stroke volume, diastolic coronary blood flow velocity and pressure-work index (calculated myocardial oxygen consumption) and decreased systemic vascular resistance and diastolic coronary vascular resistance. Mean arterial pressure and left ventricular systolic and end-diastolic pressures were unchanged. Dobutamine-induced increases in heart rate and pressure-work index were attenuated by zatebradine. Dobutamine alone increased preload recruitable stroke work slope (63 ± 6 to 116 ± 11 mmHg) and + dP dt . These positive inotropic effects were unaffected by zatebradine. Dobutamine decreased the time constant of isovolumic relaxation (30 ± 3 to 25 ± 2 ms). Dobutamine-induced decreases in the time constant of isovolumic relaxation were not altered by zatebradine, indicating that changes in the time constant occurred independent of heart rate. Dobutamine also increased the maximal segment lengthening velocity to a similar degree in zatebradine-treated versus untreated dogs. Control of dobutamine-induced tachycardia by zatebradine decreases myocardial oxygen consumption but does not alter the positive inotropic and lusitropic effects of dobutamine.

The effect of dexmedetomidine on the balance of myocardial energy requirement and oxygen supply and demand.

The effect of the alpha(2)-adrenergic agonist dexmedetomidine on the balance between myocardial energy requirement and oxygen supply and demand was investigated in 16 open-chest dogs anesthetized with either chloralose/urethane (CU) or fentanyl/halothane (FH). Myocardial energy requirement (estimated from the pressure work index), blood flow and its transmural distribution (radioactive microspheres), as well as myocardial oxygen and lactate extraction, were measured before and after administration of dexmedetomidine in doses ranging from 0.1 to 10 micrograms/kg intravenously. Under CU anesthesia, dexmedetomidine decreased heart rate, arterial blood pressure, and cardiac output. During FH anesthesia, dexmedetomidine reduced heart rate and cardiac output whereas arterial blood pressure increased. Dexmedetomidine decreased myocardial energy requirement only during CU anesthesia; myocardial oxygen supply and demand decreased in parallel. At the (large) dose of 10 micrograms/kg, myocardial oxygen extraction increased during both types of anesthesia. Dexmedetomidine >/= 1 microgram/kg increased endocardial/epicardial blood flow ratio during FH anesthesia. These data indicate that dexmedetomidine >/= 1 microgram/kg reduces myocardial energy requirements, especially when baseline heart rate and blood pressure are increased. Dexmedetomidine preserves endocardial perfusion and reduces oxygen demand in parallel with oxygen supply and energy requirements.

Comparison of the effects of levosimendan, pimobendan, and milrinone on canine left ventricular-arterial coupling and mechanical efficiency

We examined and compared the effects of levosimendan, a new myofilament calcium sensitizer with phosphodiesterase inhibiting activity, pimobendan, and milrinone on left ventricular-arterial coupling and mechanical efficiency in 21 experiments performed in open-chest, barbiturate-anesthetized dogs instrumented for measurement of aortic and left ventricular (LV) pressure (micromanometer-tipped catheter), +dP/dt, and LV volume (conductance catheter). Myocardial contractility was assessed with the end-systolic pressure-volume relation (Ees) and preload recruitable stroke work (Msw) generated from a series of differentially loaded LV pressure-volume diagrams. LV-arterial coupling and mechanical efficiency were determined by the ratio of Ees to effective arterial elastance (Ea; the ratio of end-systolic arterial pressure to stroke volume) and the ratio of stroke work (SW) to pressure-volume area (PVA), respectively. Levosimendan (0.75, 1.5, and 3.0 micrograms.kg-1.min-1) significantly (p < 0.05) increased heart rate, +dP/dt, and ejection fraction (EF) and decreased mean arterial pressure (MAP), pressure-work index (PWI; an estimate of myocardial-oxygen consumption), and LV systolic and end-diastolic pressures (LVSP and LVEDP) and volumes (EDV and ESV). Levosimendan-induced augmentation of myocardial contractility (Ees, Msw and +dP/dt) and reductions in LV afterload (Ea) caused increases in the Ees/Ea ratio (0.61 +/- 0.10 during control to 3.3 +/- 0.7 during the high dose) consistent with enhancement of LV-arterial coupling. Levosimendan increased SW/PVA (0.48 +/- 0.05 during control to 0.84 +/- 0.04 during the high dose), indicating this drug improves the transfer of myocardial potential energy to external work. Levosimendan also increased the ratio of SW to PWI (109 +/- 18 during control to 255 +/- 50 mmHg.min.100g during the high dose), suggesting that myocardial metabolic efficiency was improved as well. Like levosimendan, pimobendan and milrinone (10, 20, and 40 and 1.0, 2.0, and 4.0 micrograms.kg-1.min-1, respectively) increased HR, +dP/dt, EF, Ees, and Msw and decreased MAP, LVSP, LVEDP, EDV, ESV, and Ea. In contrast to levosimendan, neither agent reduced PWI. Pimobendan and milrinone caused dose-related increases in Ees/Ea, SW/PVA, and SW/PWI. The results indicate that levosimendan, pimobendan, and milrinone augment myocardial contractility, produce venous and arteriolar vasodilation, and enhance LV-arterial coupling and mechanical efficiency in open-chest, barbiturate-anesthetized dogs.

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.

The Efficacy of Amrinone or Adrenaline on Low Cardiac Output Following Cardiopulmonary Bypass in Patients with Coronary Artery Disease Undergoing Preoperative ß-Blockade

We examined 20 patients undergoing coronary bypass grafting for coronary artery disease with NYHA classifications of II and III who had been treated with beta-blocking agents. Patients were randomised for administration of either adrenaline (0.1 microgram/kg/min) or amrinone (bolus 1 mg/kg, continuous infusion of 5-10 micrograms/kg/min), if following cardiopulmonary bypass their cardiac index was < 2.4 L/min/m2 with normal peripheral resistance and normal or increased right- or left-ventricular filling pressures. Over a period of 1 hour, the hemodynamic parameters mean arterial pressure (MAP), cardiac index (CI), heart rate (HR), coronary perfusion pressure (CPP), total peripheral resistance (TPR), as well as the pressure-work index (PWI) were registered or calculated. By means of a coronary sinus catheter myocardial arterio-venous oxygen content difference (AVDO2cor), myocardial blood flow (MBF), using the thermodilution method, and myocardial oxygen consumption (MVO2) could be measured or calculated. Simultaneously, arterial and myocardial lactate concentrations and, using the arterio-venous lactate ratio, myocardial lactate extraction or production were quantified. Using a transseptal approach, the left-ventricular pressure curve was measured and used to differentiate for myocardial contractility (dp/dtmax). Following induction of anesthesia and after cardiopulmonary bypass, plasma levels of the used beta-blocking agent were determined. Both substances caused a significant increase in myocardial contractility, with adrenaline showing a more potent effect than amrinone. Both substances caused a significant increase in CI with a mild increase in HR. Amrinone caused a significant drop in TPR, while MAP remained practically constant.(ABSTRACT TRUNCATED AT 250 WORDS)

Dexmedetomidine partially attenuates the sympathetically mediated systemic and coronary hemodynamic effects of cocaine.

The hemodynamic effects of cocaine may be modulated by drugs which interact with central and peripheral adrenoceptors. This investigation examined the systemic and coronary hemodynamic effects of cocaine in conscious dogs with and without premedication with dexmedetomidine (DM). Three groups consisting of 24 experiments were performed using eight dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experiment days, systemic and coronary hemodynamics were recorded after cocaine (0.5 mg/kg intravenously [I.V.]) with or without DM pretreatment (2 or 4 micrograms/kg I.V.). Cocaine caused increases in heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, dP/dtmax, cardiac output, systemic vascular resistance, and pressure-work index in conscious dogs. Pretreatment with DM attenuated increases in heart rate, dP/dtmax, cardiac output, and pressure-work index produced by cocaine. Systemic vascular resistance increased after the administration of cocaine with and without DM pretreatment; however, systemic vascular resistance remained higher after cocaine in DM-pretreated dogs compared to untreated dogs. Increases in diastolic coronary vascular resistance, but no change in coronary flow velocity, were observed with cocaine alone. In contrast, cocaine increased diastolic coronary blood flow velocity without change in diastolic coronary vascular resistance when administered after DM. The results indicate that increases in heart rate, myocardial contractility, and myocardial oxygen consumption caused by cocaine were attenuated by DM pretreatment. However, cocaine-induced increases in systemic vascular resistance were augmented by DM, suggesting an additive effect at peripheral vascular alpha adrenoceptors.

Dexmedetomidine Partially Attenuates the Sympathetically Mediated Systemic and Coronary Hemodynamic Effects of Cocaine

The hemodynamic effects of cocaine may be modulated by drugs which interact with central and peripheral adrenoceptors.This investigation examined the systemic and coronary hemodynamic effects of cocaine in conscious dogs with and without premedication with dexmedetomidine (DM). Three groups consisting of 24 experiments were performed using eight dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dtmax, diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experiment days, systemic and coronary hemodynamics were recorded after cocaine (0.5 mg/kg intravenously [I.V.]) with or without DM pretreatment (2 or 4 micro gram/kg I.V.). Cocaine caused increases in heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, dP/dtmax, cardiac output, systemic vascular resistance, and pressure-work index in conscious dogs. Pretreatment with DM attenuated increases in heart rate, dP/dtmax, cardiac output, and pressure-work index produced by cocaine. Systemic vascular resistance increased after the administration of cocaine with and without DM pretreatment; however, systemic vascular resistance remained higher after cocaine in DM-pretreated dogs compared to untreated dogs. Increases in diastolic coronary vascular resistance, but no change in coronary flow velocity, were observed with cocaine alone. In contrast, cocaine increased diastolic coronary blood flow velocity without change in diastolic coronary vascular resistance when administered after DM. The results indicate that increases in heart rate, myocardial contractility, and myocardial oxygen consumption caused by cocaine were attenuated by DM pretreatment. However, cocaine-induced increases in systemic vascular resistance were augmented by DM, suggesting an additive effect at peripheral vascular alpha adrenoceptors. (Anesth Analg 1995;80:114-21)

Systemic and coronary hemodynamic effects of repetitive cocaine administration in conscious dogs.

The cardiovascular actions of cocaine are complex, and previous studies suggest that tachyphylaxis to the positive chronotropic and pressor effects of cocaine may develop after repetitive administration. We examined changes in systemic and coronary hemodynamics when single or multiple doses of intravenous (i.v.) cocaine were administered to conscious dogs. Dogs were chronically instrumented for measurement of aortic blood pressure (BP) and left ventricular pressure (LVP), LV dP/dtmax and dP/dt50, subendocardial segment length (%SS), diastolic coronary blood flow (CBF) velocity, and cardiac output (CO). Myocardial oxygen consumption was estimated by the pressure-work index (PWI). In one series of experiments, a single dose of cocaine (0.1, 0.2, 0.4, 0.8, or 1.6 mg/kg) was administered on 5 consecutive days in random fashion and peak changes in systemic and coronary hemodynamics were recorded. These doses were then randomly repeated in a second group of experiments with a 1-h interval between doses on the same day. Peak and steady-state changes in cardiovascular variables were recorded within and between each dose, respectively. In other experiments, higher doses of cocaine (0.8 or 1.6 mg/kg; separate groups) were administered four times at 1-h intervals in the same dogs and peak and steady-state changes in hemodynamics were determined. Cocaine caused dose-related increases in heart rate (HR), mean arterial pressure (MAP), LV systolic pressure (LVSP) and end-diastolic pressure (LVEDP), PWI, CO, and diastolic coronary vascular resistance and decreases in %SS when administered on different days. Cocaine also caused significant increases in baseline HR, MAP, LVSP, and PWI between doses given on the same day at 1-h intervals, but the absolute value of the peak response to cocaine of these hemodynamic parameters was independent of dosing regimen. These results were confirmed when we administered four doses of 0.8 mg/kg cocaine at 1-h intervals. The results indicate that baseline changes in systemic hemodynamic variables are a predominant feature of repetitive administration of lower doses of cocaine (< or = 0.8 mg/kg), but administration of higher doses of cocaine (> or = 8 mg/kg) at 1-h intervals caused tachyphylaxis to the hypertensive actions and myocardial oxygen consumption effects of cocaine.

Hemodynamic and mechanical determinants of myocardial O2 consumption in normal human heart: effects of dobutamine.

The relationship of myocardial O2 consumption (MVO2) to its potential hemodynamic and mechanical determinants was investigated in eight healthy normal volunteers at rest and during infusion of dobutamine (5-10 micrograms.kg-1.min-1). MVO2 was calculated from the monoexponential myocardial clearance of [1-11C]acetate with positron emission tomography, and left ventricular mechanical function was assessed by two-dimensional echocardiography. Infusion of dobutamine increased heart rate by 53%, the tension-time index by 31%, and the rate-pressure product by 116%. Cardiac output (+70%), left ventricular ejection fraction (+24%), total mechanical energy [systolic pressure-volume area, (PVA) +84%], and left ventricular pressure-work index (+100%) also increased during infusion of dobutamine. During infusion of dobutamine, MVO2 increased from 96 +/- 17 to 233 +/- 19 J.min-1.100 g left ventricle-1, while myocardial efficiency (the ratio of PVA to MVO2) decreased from 46 +/- 8 to 35 +/- 4% (P < 0.001 each). MVO2 was best correlated (P < 0.001) with the PVA (r = 0.92) and the pressure-work index (r = 0.92). Infusion of dobutamine also resulted in a significant parallel upward shift of the PVA-MVO2 relationship, indicative of an increase in PVA-independent MVO2. Our data indicate that, in human subjects, MVO2 is mainly related to systolic PVA and that inotropic stimulation with dobutamine results in decreased efficiency of contraction, such as that previously described in isolated hearts.

Dexmedetomidine Alters the Hemodynamic Effects of Desflurane and Isoflurane in Chronically Instrumented Dogs

Previous studies have shown that desflurane and isoflurane produce similar hemodynamic actions. This investigation examined the cardiovascular effects of desflurane and isoflurane in the presence or absence of dexmedetomidine, a highly selective alpha 2-adrenergic agonist that may be clinically useful as a premedicant or anesthetic adjuvant. Four groups, comprising 40 experiments, were performed using ten dogs that were chronically instrumented for measurement of aortic and left ventricular pressure, the maximum rate of increase of left ventricular pressure (dP/dtmax), diastolic coronary blood flow velocity, cardiac output, and subendocardial segment length. On separate experimental days, systemic and coronary hemodynamics were recorded, and plasma concentrations of catecholamines were measured with or without oral dexmedetomidine pretreatment (30 micrograms/kg) in the conscious state and after 15 min of equilibration at 1.0, 1.3, and 1.6 end-tidal MAC desflurane or isoflurane in a random fashion. In conscious dogs, dexmedetomidine significantly decreased heart rate, cardiac output, percent segment shortening (%SS), left ventricular dp/dtmax, myocardial oxygen consumption (as estimated by the pressure-work index), and plasma norepinephrine concentration. Concomitant increases in systemic and diastolic coronary vascular resistance were observed. Pretreatment with dexmedetomidine decreased peak increases in heart rate during desflurane and isoflurane anesthesia. Mean arterial pressure was reduced less by desflurane than by isoflurane in the absence of dexmedetomidine. This difference was abolished in dogs pretreated with dexmedetomidine. Desflurane, but not isoflurane, decreased cardiac output in dexmedetomidine-pretreated dogs when compared with untreated dogs. Concomitantly, systemic vascular resistance was greater in desflurane- versus isoflurane-anesthetized dogs pretreated with dexmedetomidine. No differences in myocardial contractility, as assessed by left ventricular dP/dtmax and %SS, were observed between desflurane and isoflurane groups in the absence or presence of dexmedetomidine. The results indicate that the cardiovascular actions of desflurane or isoflurane are similar in the absence or presence of dexmedetomidine; however, some differences between anesthetic groups were noted. In the presence of dexmedetomidine, systemic vascular resistance during desflurane anesthesia was higher when compared with that during isoflurane anesthesia, indicating that desflurane produces less pronounced direct effects on peripheral vascular tone. The concomitant greater reductions in cardiac output are consistent with greater impedance to left ventricular outflow in desflurane-anesthetized dogs pretreated with dexmedetomidine, because no differences in contractile function were observed between volatile anesthetics. In contrast, cardiac output during isoflurane anesthesia after pretreatment with oral dexmedetomidine is better maintained secondary to the peripheral vasodilator actions of this agent.

Cocaine Depresses Myocardial Contractility and Prolongs Isovolumetric Relaxation in Conscious Dogs with Partial Autonomic Nervous System Blockade

The direct effects of cocaine on myocardial contractility and isovolumetric relaxation were investigated in conscious dogs (n = 8) chronically instrumented for measurement of hemodynamics, including left ventricular pressure (LVP) and subendocardial segment length. Experiments were performed in the presence of pharmacologic blockade of beta-adrenergic, cholinergic, and ganglionic receptors because cocaine indirectly produces significant alterations in systemic hemodynamics through central and peripheral sympathomimetic actions. Myocardial contractility was quantitated using the preload recruitable stroke work (PRSW) versus end-diastolic segment length (EDL) relationship. LVP-segment length loops were generated in the unsedated control state and after cocaine administration with use of preload reduction by abrupt inferior vena caval constriction, and PRSW versus EDL slope (Mw) and length intercept (Lw) were calculated. In addition, regional preload recruitable work area (PRWA) and stroke work at constant EDL (SWEDL) were also determined. Ventricular relaxation was assessed using a time constant of isovolumetric relaxation assuming a nonzero asymptote of LVP decay. Systemic hemodynamics, myocardial contractility, and isovolumetric relaxation were recorded and calculated before and 1, 3, 5, and 10 min after cocaine administration (2 mg/kg intravenously, i.v.). Mw was significantly (p less than 0.05) reduced by cocaine (63 +/- 8 during control to 45 +/- 8 mm Hg at 1 min after drug administration). PRWA also reflected significant decreases in myocardial contractility after cocaine administration (1,800 +/- 260 during control to 1,200 +/- 220 mm Hg.mm2 at 1 min after drug administration). Similar results were observed with SWEDL (469 +/- 60 during control to 317 +/- 52 mm Hg.mm at 1 min after cocaine administration). All three indexes of contractile state demonstrated complete recovery of contractile function by 10 min after cocaine administration. The time constant of isovolumetric relaxation was prolonged by cocaine (35 +/- 2 during control to 46 +/- 3 ms at 3 min after drug administration), indicating impairment of diastolic function. Ventricular relaxation returned to control levels within 5 min after cocaine administration. No cocaine-induced alterations in coronary blood flow (CBF) or changes in calculated pressure work index (PWI, an indicator of myocardial O2 consumption) were observed. The present results suggest that cocaine produces direct negative inotropic and lusitropic effects independent of changes in myocardial O2 supply and demand and autonomic nervous system activity in conscious chronically instrumented dogs.

Changes in hemodynamics and coronary blood flow during left ventricular assistance with the hemopump

The Hemopump, a catheter-mounted left ventricular assist device, has been demonstrated to be effective in supporting patients with potentially reversible cardiac failure. The mechanism of recovery of the hearts with this device is not fully understood. The effects of the Hemopump on hemodynamics and coronary blood flow with and without myocardial ischemia and failure have been studied in S anesthetized open-chest dogs. Coronary blood flow in the left circumflex artery was assessed with an intracoronary Doppler catheter. Myocardial ischemia was induced by ligation of the left anterior descending and diagonal branches. The effects of maximum support were compared with those of minimum support. The effects of the Hemopump varied according to cardiac function. When cardiac dysfunction was mild, the Hemopump support slightly reduced myocardial O 2 demand (assessed by pressure-work index) by volume unloading. When cardiac dysfunction was severe, total bypass was achieved and myocardial O 2 demand decreased by 45%, owing to both volume and pressure unloading. Coronary blood flow was incompletely autoregulated, and the ratio of blood flow to O 2 demand increased.

Isoflurane Causes Only Minimal Increases in Coronary Blood Flow Independent of Oxygen Demand

Studies on the coronary circulation during halothane or isoflurane anesthesia are conflicting. Also, little attention has been paid to the time course of the effect of these agents on the coronary circulation. Therefore, we investigated the direct and temporal effects of halothane and isoflurane on coronary hemodynamics in chronically instrumented dogs, in the presence and absence of autonomic nervous system blockade. On different days anesthesia was induced via inhalation with 5% halothane or isoflurane in 100% oxygen. After tracheal intubation, anesthesia was maintained at 1.0 MAC for 30 min. Hemodynamics were recorded continuously. Myocardial oxygen consumption was estimated from the pressure-work index. A total of 36 experiments (four sets of experiments) were completed using nine chronically instrumented dogs. Induction of anesthesia with halothane caused a significant (P less than 0.05) increase in coronary blood flow (from 40 +/- 6 to 68 +/- 11 ml/min), which reached a peak at 1.4 +/- 0.3 min. These changes were secondary to increases in heart rate, arterial pressure, and pressure-work index (10.2 +/- 1.4 to 15.9 +/- 0.8 ml O2.min-1.100g-1). With autonomic nervous reflexes eliminated, halothane caused no change in coronary blood flow. Inhalation of isoflurane caused a greater (P less than 0.05) increase in coronary blood flow (from 39 +/- 6 to 85 +/- 14 ml/min) than did halothane; flow reached a peak at 1.8 +/- 0.6 min. With autonomic reflexes eliminated, isoflurane continued to produce an increase (P less than 0.05) in coronary blood flow (from 39 +/- 4 to 53 +/- 5 ml/min), which reached a peak at 2.1 +/- 0.4 min.(ABSTRACT TRUNCATED AT 250 WORDS)