To examine the role of nitric oxide in the beta-adrenergic vasodilation of epicardial coronary arteries in dogs, 12 dogs were instrumented for measurement of left anterior descending coronary artery diameter by transthoracic echocardiography before and after dobutamine (5 microg/kg/min IV) with and without intracoronary infusion of NG-monomethyl-L-arginine (L-NMMA) (1 mg/kg). In all 12 dogs, the diameter of left anterior descending coronary artery increased significantly from 2.35 +/- 0.25 mm to 2.59 +/- 0.24 mm (P<0.001) after dobutamine administration. In 6 of the 12 dogs, the percent change in left anterior descending coronary artery diameter induced by dobutamine decreased significantly from 12.5% +/- 8.6% to -1.5% +/- 5.4% (P<0.05) after the administration of intracoronary L-NMMA (1 mg/kg for 5 min) to block nitric oxide synthesis from L-arginine. The study demonstrated that nitric oxide formation contributes to the beta-adrenergic dilatory response of epicardial coronary arteries to dobutamine in dogs.
Adrenergic beta-Agonists ; pharmacology ; Animals ; Coronary Vessels ; physiology ; Dobutamine ; pharmacology ; Dogs ; Echocardiography ; Female ; Male ; Nitric Oxide ; physiology ; Receptors, Adrenergic, beta ; physiology ; Vasodilation ; physiology ; omega-N-Methylarginine ; pharmacology

OBJECTIVEPatient with myocardial bridging (MB) usually has a benign prognosis, but some MB patients might experience myocardial ischemia, infarction and sudden cardiac death, especially during active physical activities. The purpose of the study was to study the stress-induced blood flow changes of the mural coronary artery in MB patients determined by intracoronary Doppler.

METHODSIn 8 patients with MB, the basic average peak velocity (bAPV), hyperemic average peak velocity (hAPV) of blood flow, coronary flow reverse (CFR) proximal and distal to the mural coronary artery were measured before and during intravenously dobutamine (10 microg kg-1 min-1, then add 10 microg kg-1 min-1 at 3 min interval till 40 microg kg-1 min-1) by intracoronary Doppler.

RESULTSThe baseline mural coronary diameter reduction was (51.7+/-21.4)% and significantly increased to (90.0+/-12.7)% (P<0.01) during dobutamine infusion. bAPV on the segments proximal and distal to the mural coronary artery significantly increased from (19.83+/-5.84) cm/s and (20.75+/-4.91) cm/s to (31.52+/-10.93) cm/s and (30.46+/-9.01) cm/s (all P<0.05 vs. baseline) respectively post dobutamine infusion. CFR measured at proximal and distal to myocardial bridging also significantly decreased from (2.91+/-0.62) and (2.46+/-0.82) to (2.17+/-0.66) and (1.83+/-0.51) (all P<0.01).

CONCLUSIONStress can significantly increase the compression of intramural coronary artery and reduce CFR on coronary segments both proximal and distal to the MB. Thus, active exercise might induce myocardial ischemia in patients with myocardial bridging.

Blood Flow Velocity ; Cardiotonic Agents ; pharmacology ; Coronary Circulation ; drug effects ; Coronary Vessel Anomalies ; physiopathology ; Coronary Vessels ; drug effects ; Dobutamine ; pharmacology ; Female ; Humans ; Male ; Middle Aged

PURPOSE: Functional mitral regurgitation (FMR) and myocardial dyssynchrony commonly occur in patients with dilated cardiomyopathy (DCM). The aim of this study was to elucidate changes in FMR in relation to those in left ventricular (LV) dyssynchrony as well as geometric parameters of the mitral valve (MV) in DCM patients during dobutamine infusion. MATERIALS AND METHODS: Twenty-nine DCM patients (M:F=15:14; age: 62+/-15 yrs) with FMR underwent echocardiography at baseline and during peak dose (30 or 40 ug/min) of dobutamine infusion. Using 2D echocardiography, LV end-diastolic volume, end-systolic volume (LVESV), ejection fraction (EF), and effective regurgitant orifice area (ERO) were estimated. Dyssynchrony indices (DIs), defined as the standard deviation of time interval-to-peak myocardial systolic contraction of eight LV segments, were measured. Using the multi-planar reconstructive mode from commercially available 3D image analysis software, MV tenting area (MVTa) was measured. All geometrical measurements were corrected (c) by the height of each patient. RESULTS: During dobutamine infusion, EF (28+/-8% vs. 39+/-11%, p=0.001) improved along with significant decrease in cLVESV (80.1+/-35.2 mm3/m vs. 60.4+/-31.1 mm3/m, p=0.001); cMVTa (1.28+/-0.48 cm2/m vs. 0.79+/-0.33 cm2/m, p=0.001) was significantly reduced; and DI (1.31+/-0.51 vs. 1.58+/-0.68, p=0.025) showed significant increase. Despite significant deterioration of LV dyssynchrony during dobutamine infusion, ERO (0.16+/-0.09 cm2 vs. 0.09+/-0.08 cm2, p=0.001) significantly improved. On multivariate analysis, DeltacMVTa and DeltaEF were found to be the strongest independent determinants of DeltaERO (R2=0.443, p=0.001). CONCLUSION: Rather than LV dyssynchrony, MV geometry determined by LV geometry and systolic pressure, which represents the MV closing force, may be the primary determinant of MR severity.
Aged ; Dobutamine/administration & dosage/*pharmacology ; Echocardiography ; Female ; Humans ; Male ; Middle Aged ; Mitral Valve/*anatomy & histology/drug effects/*physiopathology ; Mitral Valve Insufficiency/*physiopathology ; Ventricular Dysfunction, Left/*physiopathology

The purpose of this study was to evaluate the efficacy of adenosine triphosephate (ATP) in comparison to sodium nitroprusside (SNP) in reducing left ventricular afterload in 20 patients, ASA physical status I, during ethrane-N2O anesthesia. Hemodynamic effects of intravenous ATP (30~250 ug/kg/min) were compared with those of SNP (0.3~2.5 ug/kg/min) in group 1 (n=10). In group 2 (n=10), hemodynamic and intrapulmonary shunt effects of dobutamine (1 ug/kg/min) alone and in combination with ATP or SNP, required to maintain mean arterial pressure around 70 mmHg, were compared. The results were as follows. 1) Both ATP and SNP reduced arterial pressure rapidly resulting from a marked decrease in systemic vascular resistance in a dose-related manner. 2) Cardiac index increased from 3.31+/-0.201/min/m2 to 4.04+/-0.281/min/m2 (p<0.01) following dobutamine alone, and increased further to 5.71+/-0.38 1/min/m2 (p<0.001) and decreased to 3.77+/-0.28 1/min/m (NS) in combination with ATP and SNP, respectively. 3) At equivalent decrease in mean arterial pressure, ATP increased heart rate significantly less than SNP. 4) Hypotensive response was more stable during ATP infusion than during SNP infusion. 5) Arterial oxygen tension was significantly higher during dobutamine/ATP infusion than during dobutamine/SNP infusion (268+/-6 vs 256+/-9 mmHg, p<0.05). 6) Intrapulmonary shunt fraction increased from 4.49+/-0.65% to 5.51+/-0.71% (p<0.05) following dobutamine alone, and increased further to 9.92+/-1.13 (p<0.001) and to 7.21+/-0.77% (p<0.01) in combination with ATP and SNP, respectively. These results suggest, although ATP increases intrapulmonary shunt fraction more than does SNP, ATP has significant advantage over SNP, either alone or in combination with dobutamine, in improving cardiac performance in patients with low output states due to high peripheral vascular resistance.
Adenosine Triphosphate* ; Adenosine* ; Anesthesia ; Arterial Pressure ; Dobutamine* ; Heart Rate ; Hemodynamics* ; Humans ; Lung ; Nitroprusside* ; Oxygen ; Pharmacology ; Sodium* ; Sympathetic Nervous System ; Vascular Resistance

To evaluate the effects of left ventricular contractility on the changes of average image intensity (AII) of the myocardial integrated backscatter (IB) and cyclic variation in IB (CVIB), 7 adult mongrel dogs were studied. The magnitude of AII and CVIB were measured from myocardial IB carves before and after dobatamine or propranolol infusion. Dobutamine or propranolol did not affect the magnitude of AII (13.8 +/- 0.7 vs 14.7 +/- 0.5, P > 0.05 or 14.3 +/- 0.5 vs 14.2 +/- 0.4, P > 0.05). However, dobutamine produced a significant increase in the magnitude of CVIB (6.8 +/- 0.3 vs 9.5 +/- 0.6, P < 0.001) and propranolol induced significant decrease in the magnitude of CVIB (7.1 +/- 0.2 vs 5.2 +/- 0.3, P < 0.001). The changes of the magnitude of AII and CVIB in the myocardium have been demonstrated to reflect different myocardial physiological and pathological changes respectively. The alteration of contractility did not affect the magnitude of AII but induced significant change in CVIB. The increase of left ventricular contractility resulted in a significant rise of the magnitude of CVIB and the decrease of left ventricular contractility resulted in a significant fall of the magnitude of CVIB.
Adrenergic beta-Agonists ; pharmacology ; Adrenergic beta-Antagonists ; pharmacology ; Animals ; Coronary Circulation ; Dobutamine ; pharmacology ; Dogs ; Echocardiography ; methods ; Hemodynamics ; drug effects ; Myocardial Contraction ; drug effects ; physiology ; Propranolol ; pharmacology ; Systole ; Ventricular Function, Left ; physiology

OBJECTIVETo evaluate the direct effects of dobutamine as compared to adenosine on the coronary microcirculation in both normal and stenotic segments using myocardial contrast echocardiography (MCE).

METHODSLeft anterior descending (LAD) coronary artery stenosis, which was not flow limiting at rest, was established in 9 dogs. At the baseline and during intracoronary infusion of dobutamine (2 mg.kg(-1).min(-1)) and adenosine (5 mg.kg(-1).min(-1)), the radiolabeled microsphere (RM)-derived myocardial blood flow (MBF) were determined, and the double product (DP) and myocardial vascular resistance (MVR) were calculated. MCE was performed to determine the myocardial blood volume (MBV, represented by A) and microbubble velocity (beta).

RESULTSAs compared to the baseline level, the MBF increased and MVR decreased significantly in both the normal and abnormal beds during infusion of both drugs (P<0.05). In the normal bed, adenosine had no effect on MBV, the decrease in MVR was the result of decreased arteriolar (plus venular) resistance, and the increase in MBF was predominately due to the increase in b (deltabeta/ deltaA=13.6). Dobutamine caused a 28% increase in MBV, responsible for 32% of the decrease in the total MVR, but the increase in MBF arose mainly from the increase in b (deltabeta/deltaA=5.9). In the abnormal bed, both the drugs caused a similar increase in MBF entirely by increasing b, and 14% and 15% of the increases in capillary resistance were associated with the capillary derecruitment during administration of dobutamine and adenosine, respectively.

CONCLUSIONThe direct effects of intracoronary dobutamine infusion on the coronary microcirculation are similar to that of adenosine, and the increase in MBF occurs mostly as the result of increased myocardial blood velocity.

Adenosine ; pharmacology ; Adrenergic beta-Agonists ; pharmacology ; Animals ; Blood Flow Velocity ; drug effects ; Coronary Circulation ; drug effects ; Coronary Stenosis ; diagnostic imaging ; Coronary Vessels ; diagnostic imaging ; Dobutamine ; pharmacology ; Dogs ; Echocardiography ; methods ; Microcirculation ; drug effects ; Vasodilator Agents ; pharmacology

The objective of this study was to develop a pre-clinical large animal model for the in vivo hemodynamic testing of prosthetic valves in the aortic position without the need for cardiopulmonary bypass. Ten male pigs were used. A composite valved conduit was constructed in the operating room by implanting a prosthetic valve between two separate pieces of vascular conduits, which bypassed the ascending aorta to the descending aorta. Prior to applying a side-biting clamp to the ascending aorta for proximal grafting to the aortic anastomosis, an aorta to femoral artery shunt was placed just proximally to this clamp. The heart rate, cardiac output, Vmax, transvalvular pressure gradient, effective orifice area and incremental dobutamine stress response were assessed. A dose dependant increase with dobutamine was seen in terms of cardiac output, Vmax, and the peak transvalvular pressure gradient both in the native and in the prosthetic valve. However, the increment was much steeper in the prosthetic valve. No significant differences in cardiac output were noted between the native and the prosthetic valves. The described pre-clinical porcine model was found suitable for site-specific in-vivo hemodynamic assessment of aortic valvular prosthesis without cardiopulmonary bypass.
Adrenergic beta-Agonists/pharmacology ; Animals ; Aorta/pathology ; Aortic Valve/*pathology ; Disease Models, Animal ; Dobutamine/pharmacology ; Dose-Response Relationship, Drug ; Heart Rate ; *Heart Valve Prosthesis ; Male ; Pressure ; *Prosthesis Implantation ; Support, Non-U.S. Gov't ; Swine ; Thoracic Arteries/pathology