Diastolic Coronary Blood Flow Velocity Research Articles

Reversible impairment of coronary flow reserve in acute myocarditis.

Acute myocarditis is accompanied by an impaired coronary microcirculation. These microcirculatory disturbances are not well defined, and data are derived from complex invasive measurements. Therefore, this study aimed to evaluate the inflammation-induced microcirculatory dysfunction including its reversibility and association with markers of inflammation severity (extent of LGE on CMR imaging and laboratory markers of myocardial necrosis) using the noninvasive technique of echocardiographic CFR measurement. Patients (n=14) with clinically suspected acute myocarditis in the absence of coronary artery disease were prospectively enrolled, and echocardiographic CFR was determined by measuring peak diastolic coronary blood flow velocity at rest (PDV1) and under adenosine-induced hyperemia (PDV2) at baseline and 3-month follow-up. Eight of 14 (57.1%) patients showed an impaired baseline CFR (PDV2/PDV1<2). These patients were characterized by higher levels of cardiac troponin T (0.55±0.39 vs 0.18±0.08; P=0.008) and larger areas of LGE on CMR. At 3-month follow-up, CFR was normal in all patients. A reversibly impaired coronary microcirculation is a frequent finding in acute myocarditis and is associated with markers of inflammation severity. Echocardiographic CFR measurement represents a feasible and safe method for its assessment.

Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X

The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known. We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P < 0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P < 0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P < 0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P < 0.01 for both) after adjustment for all CVRFs, including serum CRP levels. In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Abstract 5518: Abnormal Coronary Flow Reserve is Related to Impairment of Left Ventricular Function During Adenosine Stress Echocardiography in Untreated Hypertensive Patients

Objective: Coronary microcirculation is disturbed in hypertensive patients. We investigated the effects of coronary flow reserve (CFR) on the response of Left Ventricular (LV) systolic and diastolic function as assessed by Tissue Doppler Imaging during adenosine stress echocardiography in never-treated hypertensive patients. Methods: We studied 43 patients (mean age: 53±12 years), with untreated arterial hypertension (clinic blood pressure &gt;140/90 mmHg and &gt;125/80 mmHg in 24hour ambulatory BP monitoring) by adenosine stress echocardiography and 22 healthy controls matched for sex, age and atherosclerotic factors. We measured: time integral (VTI-Vd) of diastolic (Vd) coronary blood flow velocity by transthoracic Doppler echocardiography of the LAD Ratio of VTI-Vd after adenosine infusion (140 μ g/kg/min) to VTI-Vd at baseline to assess CFR E and A doppler, Sm, Em, Am lateral mitral annulus velocities with TDI, Em/Am ratio and E/Em ratio before and during adenosine infusion to assess LV systolic and diastolic function, the percent % changes of the measured indices between baseline and peak adenosine infusion. Results: All patients had normal baseline ejection fraction. Compared to controls, hypertensives had lower CFR (2.3±0.7 vs. 2.9±0.9, p=0.03). At baseline, hypertensives compared to controls, had lower Em/Am ratio (0.9±0.3 vs. 1.3±0.4, p=0.002), Sm (8.7±1.7 vs. 9.7±2.6, p=0.07), Em (10.1±2.8 vs 12.1±3.5, p=0.03) and higher Am (11.1±2.5 vs. 9.5±2.0, p=0.03). At peak adenosine infusion there were an increase in Sm, Em and Am in all patients (p&lt;0.05). Furthermore a decreasing CFR was associated with a decreasing Em (r= 0.46, p=0.05), Em/Am (r=0.49, p=0.048) and increasing E/Em (r=−0.4, p=0.04). A reduced CFR was related with a smaller % increase of Sm (r= −0.40, p=0.049), % increase of Em (r=− 0.5, p=0.033) and higher % increase of E/Em (r=−.42, p=0.04) at peak stress. Patients with CFR&lt;2.5 (n=28), compared to those with CFR≥2.5 had lower % change of Sm (27±20% vs. 51±34% p=0.04), % change of Em (8±3% vs. 46 ±3%, p=0.05) and higher % increase of E/Em (24±3% vs −1±2%, p=0.04). Conclusions: An abnormal response of LV function during adenosine stress echocardiography is related with impaired CFR in untreated hypertensive patients.

Vasoconstriction seen in coronary bypass grafts during handgrip in humans

In animal studies, sympathetically mediated coronary vasoconstriction has been demonstrated during exercise. Human studies examining coronary artery dynamics during exercise are technically difficult to perform. Recently, noninvasive transthoracic Duplex ultrasound studies demonstrated that 1) patients with left internal mammary artery (LIMA) grafts to the left anterior descending artery can be imaged and 2) the LIMA blood flow patterns are similar to those seen in normal coronary arteries. Accordingly, subjects with LIMA to the left anterior descending artery were studied during handgrip protocols as blood flow velocity in the LIMA was determined. Beat-by-beat analysis of changes in diastolic coronary blood flow velocity (CBV) was performed in six male clinically stable volunteers (60 +/- 2 yr) during two handgrip protocols. Arterial blood pressure (BP) and heart rate (HR) were also measured, and an index of coronary vascular resistance (CVR) was calculated as diastolic BP/CBV. Fatiguing handgrip performed at [40% of maximal voluntary contraction (MVC)] followed by circulatory arrest did not evoke an increase in CVR (P = not significant). In protocol 2, short bouts of handgrip (15 s) led to increases in CVR (18 +/- 3% at 50% MVC and 20 +/- 8% at 70% MVC). BP was also increased during handgrip. Our results reveal that in conscious humans, coronary vasoconstriction occurs within 15 s of onset of static handgrip at intensities at or greater than 50% MVC. These responses are likely to be due to sympathetic vasoconstriction of the coronary circulation.

Assessment of Coronary Vasodilatation in Response to Nitroglycerin with Transthoracic Doppler Echocardiography

Previous studies demonstrated impaired coronary vasodilatory response (VR) to nitroglycerin (NG) in patients with coronary atherosclerosis. We hypothesized that the effect of the NG on the coronary blood flow (CBF) is negligible compared with its effect on the epicardial coronary artery dilatation and, therefore, that CBF velocity reduction after NG can reflect the magnitude of epicardial coronary artery dilatation. Quantitative coronary angiography was performed at the left anterior descending coronary artery (LAD) before and after intracoronary NG (200 mug) infusion in 18 patients with normal-looking coronary angiogram. VR assessed by quantitative coronary angiography (VRangio) was defined as: (LAD diameter after NG)(2)/(LAD diameter before NG)(2). Mean values measured at the ostium and at the junction of mid and distal LAD were used in the analysis. Diastolic CBF velocity was evaluated by using a 7-MHz transducer at the distal LAD before and 3 minutes after sublingual NG. VR assessed by echocardiography (VRecho) was defined as: (mean diastolic CBF velocity before sublingual NG)/(mean diastolic CBF velocity after sublingual NG). In 11 patients, plaque burden was assessed by intravascular ultrasound and results were compared with VRangio and VRecho. VRecho was found to correlate well with VRangio (r = 0.71, P = .001), and VRangio and VRecho showed significant negative correlations with plaque burden (r = -0.66, P = .03; r = -0.77, P = .005, respectively). VR to NG can be evaluated noninvasively with transthoracic Doppler echocardiography.

Usefulness of coronary flow reserve over regional wall motion when added to dual-imaging dipyridamole echocardiography

Vasodilator stress echocardiography allows semi-simultaneous imaging of left anterior descending (LAD) coronary flow and regional wall function. To assess the relative (and additive?) value of regional flow and function for noninvasive identification of angiographically assessed LAD disease in patients with chest pain syndrome, we studied 230 consecutive in-hospital patients (134 men, aged 63.5 ± 11 years) with chest pain syndrome and normal regional and global left ventricular function. All patients underwent stress echocardiography with dipyridamole (up to 0.84 mg/kg over 10 minutes), including wall motion analysis by 2-dimensional echocardiography and coronary flow reserve (CFR) evaluation of the LAD artery by Doppler, with or without contrast injection. A new regional wall motion abnormality in ≥2 contiguous segments was required for 2-dimensional echocardiographic positivity. CFR was evaluated as the ratio of dipyridamole to peak diastolic coronary blood flow velocity at rest. All patients underwent coronary angiography within 60 days; a quantitatively assessed diameter reduction >50% of the LAD artery was considered significant. Of the 230 patients, 70 had LAD disease. A regional wall motion abnormality in LAD territory was present in 52 patients, and reduced CFR (<1.9) in 62 patients. Sensitivity for detecting LAD disease was 74% for 2-dimensional echocardiography (95% confidence interval [CI] 64% to 84%) and 81% for CFR <1.9 (95% CI 72% to 90%); specificity was 91% (95% CI 87% to 96%) for 2-dimensional echocardiography and 84% for CFR (95% CI 79% to 90%). Accuracy was 86% for 2-dimensional echocardiography (95% CI 82% to 91%) and 83.5% for CFR (95% CI 79% to 88%). When 2-dimensional echocardiography and CFR criteria were considered, sensitivity increased to 93% (95% CI 87% to 99%), with 80.6% specificity (95% CI 74.5% to 86.7%). CFR was assessed during vasodilator stress echocardiography. Its diagnostic accuracy for detecting LAD disease was comparable to regional wall motion abnormalities. However, the data for flow and function can be complementary in terms of predicting underlying angiographic anatomy, because abnormal wall motion can include coronary artery disease, and negative CFR can exclude it.

Two different coronary blood flow velocity patterns in thrombolysis in myocardial infarction flow grade 2 in acute myocardial infarction: Insight into mechanisms of microvascular dysfunction

ObjectivesWe sought to determine which of the two main potential mechanisms underlying Thrombolysis In Myocardial Infarction flow grade 2 (TIMI-2 flow) operate in an individual patient who has had an acute myocardial infarction (AMI). BackgroundSystolic flow reversal (SFR) is a specific finding of capillary damage, the no-reflow phenomenon. The coronary blood flow velocity (CBFV) pattern of thromboemboli, however, remains unknown. MethodsData on 105 patients with AMI (57 with anterior and 48 with nonanterior cases) who underwent a coronary intervention were analyzed. The CBFV was recorded by a Doppler guide wire, and tissue perfusion was assessed with myocardial contrast echocardiography (MCE). ResultsStudy patients were classified into three groups according to TIMI grade and the presence or absence of SFR: 1) TIMI-3 flow (n = 80); 2) TIMI-2 flow with SFR (SFR[+], n = 14); and 3) TIMI-2 flow without SFR (SFR[-], n = 11). Diastolic CBFV was the lowest in SFR(-) (TIMI-3 vs. SFR[+] vs. SFR[-]: 34 vs. 31 vs. 9 cm/s), and the systolic to diastolic CBFV ratio was also the highest in SFR(-) (0.43 vs. −0.18 vs. 0.66). The no-reflow phenomenon documented by MCE was found in all patients in the SFR(+) group, but in only one patient (10%) in the SFR(-) group. Intracoronary thrombus was more frequently found in SFR(-) than in SFR(+) (91% vs. 14%, p < 0.05). ConclusionsAt least two different CBFV patterns are noted in patients with reperfused AMI who have TIMI-2 flow. Capillary damage is mostly responsible for SFR(+), and SFR(-) is seen in thromboemboli possibly due to increased coronary arterial resistance.

The effect of verapamil on response of coronary vasomotion to handgrip exercise in symptomatic patients with hypertrophic cardiomyopathy.

To assess the effect of verapamil on the response of diastolic coronary blood flow velocity (CBFV) and coronary vascular resistance index to handgrip exercise in symptomatic HCM patients. In 13 patients with HCM, the CBFV was detected in the distal portion of left anterior descending coronary artery using high-sensitivity transthoracic Doppler echocardiography. The peak diastolic CBFV and coronary vascular resistance index (calculated as the ratio of mean aortic pressure to CBFV) was measured at baseline and during handgrip exercise. Changes of these parameters induced by the exercise (expressed as the percentage of baseline values) were compared on verapamil treatment and after verapamil withdrawal. The same measurements were obtained in 10 healthy control subject. In HCM patients, the increase in CBFV during exercise was significantly higher on than off verapamil therapy (16.2 +/- 5% versus 6.8 +/- 3.8%, p < 0.001). In healthy controls, exercise-induced increase in CBFV was comparable to CBFV changes in HCM patients receiving verapamil (17.4 +/- 5.7 versus 16.2 +/- 5%, p > 0.05) and was significantly greater than the CBFV response in HCM patients off verapamil (17.4 +/- 5.7% versus 6.8 +/- 3.8% p < 0.005). During exercise the coronary vascular resistance index decreased on verapamil and increased after drug withdrawal (-5.8 +/- 5.6% versus 1.1 +/- 5.1%, p < 0.001). In healthy controls the coronary vascular resistance index decreased during exercise -8.5 +/- 4.5% to similar extent as in HCM patients on verapamil. In HCM symptomatic patients, verapamil improved coronary vasomotor response to physical stress. Verapamil was able to restore adequate vasodilator response to handgrip exercise.

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.

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.

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)

Perfusion of Ischemic Myocardium during Anesthesia with Sevoflurane

Sevoflurane produces direct vasodilation of coronary arteries in vitro and decreases coronary vascular resistance in vivo, pharmacologic properties that may contribute to the development of "coronary steal." This investigation examined the effects of sevoflurane on the distribution of regional myocardial perfusion in chronically instrumented dogs with steal-prone coronary artery anatomy. Dogs were chronically instrumented for measurement of aortic and left ventricular pressure, diastolic coronary blood flow velocity and subendocardial segment length. After recovery from surgery, dogs underwent repetitive, brief, left anterior descending coronary artery (LAD) occlusions via an implanted hydraulic vascular occluder to enhance collateral development. A progressive left circumflex coronary artery (LCCA) stenosis was also obtained using an ameroid constrictor. After development of LCCA stenosis, the LAD was totally occluded to produce a model of multivessel coronary artery disease. Systemic hemodynamics, regional contractile function and myocardial perfusion measured with radioactive microspheres were assessed in the conscious state and during sevoflurane anesthesia at 1.0 and 1.5 MAC with and without restoration of arterial blood pressure and heart rate to conscious levels. Total LAD occlusion with simultaneous LCCA stenosis increased heart rate, mean arterial pressure, left ventricular systolic and end-diastolic pressures, end-diastolic segment length, and rate-pressure product in conscious dogs. Subsequent administration of sevoflurane caused dose-related decreases in arterial pressure, left ventricular systolic pressure, double product, and peak rate of increase of left ventricular pressure at 50 mmHg. Perfusion of normal myocardium was unchanged during sevoflurane anesthesia. In contrast, sevoflurane caused dose-dependent decreases in blood flow to myocardium supplied by the stenotic LCCA, which returned to control levels after restoration of heart rate and arterial pressure. No reduction in collaterally derived blood flow to the occluded region was produced by 1.0 or 1.5 MAC sevoflurane. No redistribution of blood flow away from the occluded LAD region to normal or stenotic myocardium occurred during sevoflurane anesthesia. In fact, increases in the ratio of blood flow between occluded and normal zones or occluded and stenotic zones were observed in the subepicardium during 1.5 MAC sevoflurane with maintenance of the heart rate and arterial pressure at conscious levels. The results demonstrate that sevoflurane does not reduce or abnormally redistribute myocardial blood flow derived from coronary collateral vessels in a chronically instrumented canine model of multivessel coronary artery obstruction.

Effect of dynamic cardiomyoplasty on phasic coronary arterial flow velocity in canine hearts

The usefulness of dynamic cardiomyoplasty has been demonstrated repeatedly, both experimentally and clinically. Although clinical applications of dynamic cardiomyoplasty to ischemic heart disease have been reported, its effect on the coronary blood flow has never been discussed. Therefore, we tested the hypothesis that dynamic cardiomyoplasty might adversely affect coronary arterial blood flow through compression of the coronary arteries during systolic skeletal muscular contraction and incomplete relaxation of the skeletal muscle flap during diastole. Dynamic cardiomyoplasty was performed in seven mongrel dogs with the use of a left latissimus dorsi muscle flap, paced synchronously with the R wave of the electrocardiogram. A 3F Doppler catheter was placed in the left main trunk of the coronary artery to assess the instantaneous changes of coronary flow velocity by fast Fourier transformation analysis. We compared systolic and diastolic properties during assisted versus unassisted cardiac cycles by calculating the peak velocity and the time-velocity integral. During assisted cardiac cycles, a significant enhancement of coronary arterial blood flow velocity was demonstrated by significant increases in both systolic and diastolic peak velocity (26.9% ± 6.5%, p < 0.005; 4.0% ± 1.6%, p < 0.05, respectively) and time-velocity integral (20.9% ± 4.8%, p < 0.05; 10.0% ± 4.6%, p < 0.05, respectively). Enhancement of coronary arterial blood flow velocity was associated with an increase in mean aortic pressure (16.4% ± 1.3%, p < 0.005) and descending aortic flow (67.5% ± 5.3%, p < 0.005). Also, the improved systolic coronary arterial blood flow velocity was consistent with an increase in systolic aortic pressure (15.8% ± 1.5%, p < 0.005), and enhancement of diastolic coronary arterial blood flow velocity was associated with an increase in diastolic aortic pressure (8.6% ± 2.3%, p < 0.01). We concluded that coronary arterial blood flow velocity was increased by the enhancement of cardiac function as a result of dynamic cardiomyoplasty, leading to an increase of coronary perfusion pressure and cardiac output. (J THORAC CARDIOVASC SURG 1994;108:609-15)

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.

Oral Dexmedetomidine Preserves Baroreceptor Function and Decreases Anesthetic Requirements of Halothane-anesthetized Dogs

The alpha 2-adrenergic agonist, dexmedetomidine, alters hemodynamics by diminishing sympathetic and/or augmenting parasympathetic neurogenic tone to the heart and peripheral vasculature. However, the specific actions of dexmedetomidine on baroreceptor function are unknown. The purpose of the current investigation was to determine baroreceptor function during an anesthetic state produced by halothane and a similar anesthetic state produced by halothane after dexmedetomidine pretreatment. Dogs were instrumented for measurement of arterial and left ventricular pressures, coronary blood flow velocity, segment shortening and cardiac output. Five experimental conditions were studied in the same dogs (n = 8). Measurements of baroreceptor sensitivity (via abrupt decreases and increases in arterial pressure resulting in changes in the cardiac cycle) and hemodynamics were made in the conscious state in dogs in conditions 1 and 2 before and after 25 and 50 micrograms.kg-1 of oral dexmedetomidine, respectively. Dogs in conditions 3 and 4 received the same doses of dexmedetomidine and were then anesthetized with halothane. Baroreceptor sensitivity was determined after 60 min of halothane anesthesia. For comparison, dogs in condition 5 had baroreceptor sensitivity measured after 60 min of halothane anesthesia in the absence of dexmedetomidine. Dexmedetomidine decreased heart rate, rate-pressure product, rate of increase of left ventricular pressure at 50 mmHg, cardiac output and percent segment shortening. Diastolic coronary vascular resistance and systemic vascular resistance were increased with both oral doses. In addition, diastolic coronary blood flow velocity and stroke volume were significantly reduced by the high dose of dexmedetomidine. Anesthesia with halothane increased heart rate and decreased mean arterial pressure, left ventricular systolic pressure, rate of increase of left ventricular pressure at 50 mmHg, stroke volume and segment shortening. Administration of dexmedetomidine before halothane anesthesia in dogs pretreated with dexmedetomidine resulted in small increases in heart rate and decreases mean arterial pressure and left ventricular systolic pressure. Both doses of dexmedetomidine demonstrated anesthetic-sparing effects. The end-tidal concentration of halothane to maintain dogs unconscious and unresponsive was reduced by 30% and 40% (1.03 +/- 0.08% to 0.67 +/- 0.09% and to 0.58 +/- 0.06% end-tidal, respectively) at 25 and 50 micrograms.kg-1, respectively. Baroreceptor sensitivity was profoundly depressed by halothane alone. Dexmedetomidine did not significantly change the slope of the baroreflex response when compared with conscious control measurements. After pretreatment with dexmedetomidine, the reduction in halothane concentration required for a comparable level of anesthesia resulted in significant preservation of baroreceptor sensitivity. The results indicate that dexmedetomidine alone does not alter baroreflex sensitivity. In addition, possibly through an anesthetic-sparing action, dexmedetomidine preserves baroreflex responses during halothane anesthesia. Such a preservation of the baroreceptor reflex by dexmedetomidine might provide an important mechanism for maintenance of cardiovascular stability by retaining buffer reflexes during general anesthesia.

Direct Negative Inotropic and Lusitropic Effects of Sevoflurane

Volatile anesthetics depress left ventricular mechanical performance during multiple phases of the cardiac cycle. The effects of sevoflurane on systolic and diastolic function have yet to be fully evaluated. This investigation characterized the systemic and coronary hemodynamic, inotropic, and lusitropic actions of sevoflurane in chronically instrumented dogs in the presence and absence of autonomic nervous system (ANS) reflexes. Because ANS activity may influence the actions of volatile anesthetics in vivo, experiments were conducted in both ANS-intact and ANS-blocked animals. Eighteen experiments were performed in nine dogs chronically instrumented for measurement of aortic and left ventricular pressure, rate of change of left ventricular pressure, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. The preload recruitable stroke work slope was used to assess myocardial contractility. Diastolic function was evaluated by a time constant of isovolumic relaxation, maximum segment lengthening velocity during rapid ventricular filling, and a regional chamber stiffness constant. Dogs were assigned to receive sevoflurane with or without pharmacologic blockade of the ANS in a random fashion. On separate experimental days, systemic and coronary hemodynamics and left ventricular pressure--segment length diagrams and waveforms were recorded in the conscious state and during sevoflurane anesthesia (1.0, 1.25, 1.5, and 1.75 MAC). In dogs with intact ANS reflexes, sevoflurane caused significant (P < 0.05) increases in heart rate and dose-related decreases in mean arterial pressure, left ventricular systolic pressure, cardiac output, and diastolic coronary vascular resistance. Sevoflurane also decreased myocardial contractility (preload recruitable stroke work slope 96 +/- 4 in the conscious state to 42 +/- 3 mmHg at 1.75 MAC). Sevoflurane prolonged isovolumic relaxation (time constant of isovolumic relaxation 35 +/- 1 in the conscious state to 51 +/- 3 ms at 1.75 MAC) and decreased rapid ventricular filling (maximum segment lengthening velocity 40.2 +/- 6.0 in the conscious state to 21.8 +/- 3.8 mm.s-1 at 1.75 MAC) without affecting regional chamber stiffness. Sevoflurane caused similar alterations in functional indices of left ventricular systolic and diastolic performance in autonomically blocked dogs. Sevoflurane caused direct negative inotropic and lusitropic effects in chronically instrumented dogs with and without ANS blockade.

Improved Doppler signal intensity in coronary arteries after intravenous peripheral injection of a lung-crossing contrast agent (SHU 508A)

Objectives. We tested the hypothesis that SHU 508A, a new lung-crossing contrast agent capable of increasing the Doppler signal to noise ratio in the right heart as well as left heart cavities after intravenous injection, could increase Doppler signal intensity in coronary arteries, thus improving the feasibility and quality of transesophageal Doppler echocardiographic evaluation of coronary blood flow velocity.Background. Coronary blood flow velocity can be evaluated by transesophageal Doppler echocardiography. However, an adequate Doppler tracing is obtainable in a relatively low percent of patients.Methods. Transesophageal Doppler echocardiography of coronary arteries was performed in 35 patients before and after SHU 508A injection at four different dosages (200 mg/ml in 5 ml, 200 mg/ml in 10 ml, 300 mg/ml in 5 ml and 300 mg/ml in 10 ml). Color Doppler mapping of coronary flow and pulsed wave Doppler measurement of coronary blood flow velocity were attempted in all patients.Results. Color Doppler flow mapping of 105 evaluated coronary segments (left main, left anterior descending and circumflex in 35 patients) was not detectable or was weak in 88% of patients before and 33% of patients after echo contrast injection (p < 0.0001); it was optimal (that is, well with complete flow mapping of the explored vessel) in only 11% of patients before and 67% after echo contrast injection (p < 0.0001). In addition, pulsed wave Doppler signal quality improved after echo contrast injection: Pulsed wave Doppler recording of coronary blood flow velocity was not obtainable or was weak in 78% of cases before and 34% after echo contrast injection (p < 0.0001); pulsed wave Doppler recording of coronary blood flow velocity was optimal (that is, there was a complete and well defined outline of diastolic coronary blood flow velocity in 23% of cases before and 66% after echo contrast injection [p < 0.0001]. Both length and width of color Doppler mapping in the left anterior descending coronary artery increased after SHU 508A injection (from 5.75 ± 532 and 1.51 ± 1.17 to 17.04 ± 8.76 and 4.21 ± 1.78 mm, respectively, mean ± SD, p < 0.0001).Conclusions. The feasibility and quality of recording coronary blood flow velocity by transesophageal Doppler echocardiograply are considerably improved by intravenous injection of SHU 508A. The improved feasibility of this new semi-invasive method for evaluating coronary blood flow velocity and flow reserve can considerably increase its research and clinical utilization.

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.

Amrinone Enhances Myocardial Contractility and Improves Left Ventricular Diastolic Function in Conscious and Anesthetized Chronically Instrumented Dogs

Volatile anesthetics depress left ventricular mechanical performance in vivo by altering intracellular calcium regulation. Although amrinone has been shown to reverse the negative inotropic effects of volatile anesthetics, the actions of amrinone on anesthetic-induced diastolic dysfunction are unknown. This investigation examined and compared the direct effects of amrinone on left ventricular systolic and diastolic function in conscious and anesthetized dogs. Experiments were conducted in the presence of pharmacologic blockade of the autonomic nervous system, because autonomic activity may influence the hemodynamic actions of volatile anesthetics and amrinone in vivo. Three groups, comprising a total of 27 experiments, were conducted using 9 dogs chronically instrumented for measurement of aortic and left ventricular pressure, left ventricular dP/dt, subendocardial segment length, diastolic coronary blood flow velocity, and cardiac output. Myocardial contractility was evaluated using the preload recruitable stroke work relationship slope (Mw). Diastolic function was characterized by a time constant of isovolumic relaxation (tau), a regional chamber stiffness constant (KT), and maximum segment lengthening velocity during rapid ventricular filling (dL/dtmax). On three separate days, an amrinone bolus of 1 mg/kg, followed by an infusion at 10, 20, 40, or 80 micrograms.kg-1.min-1, was administered. Hemodynamics and ventricular pressure-segment length loops and waveforms were recorded after a 15-min equilibration at each dose in the conscious state or during isoflurane or halothane anesthesia (1.25 MAC). In conscious dogs, amrinone significantly increased myocardial contractility in a dose-dependent manner (Mw of 65 +/- 8 to 108 +/- 10 mmHg at the high dose). Amrinone also shortened isovolumic relaxation (tau of 32.7 +/- 2.1 to 24.8 +/- 0.9 ms at the high dose) and enhanced rapid ventricular filling (dL/dtmax of 34.8 +/- 1.2 to 45.1 +/- 2.3 mm/s at the high dose) in a dose-related fashion. In addition, amrinone reduced regional chamber stiffness (Kp of 0.49 +/- 0.09 to 0.31 +/- 0.08 mm/s at the high dose) in conscious dogs. Amrinone also enhanced left ventricular systolic (increase in Mw) and diastolic function (decreases in tau and Kp and increases in dL/dtmax) when this drug was administered to dogs anesthetized with isoflurane or halothane. Amrinone produced positive inotropic and lusitropic effects in both conscious and anesthetized dogs with autonomic nervous system blockade. These results indicate that amrinone-induced improvement of left ventricular performance are related to actions in diastole, as well as systole.